Navegando por Palavras-chave "dopamine"

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    Acute mood effect of donepezil in young, healthy volunteers
    (Wiley-Blackwell, 2013-05-01) Pompeia, Sabine [UNIFESP]; Gouveia, Juliana Ramos [UNIFESP]; Fernandes Galduroz, Jose Carlos [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objective Chronic use of the acetylcholinesterase inhibitor donepezil has been found to improve mood or to induce mania/hypomania in many neuropsychiatric patients with altered cholinergic and dopaminergic tone. Our aim was to determine whether acutely administered donepezil would alter mood in volunteers with no such alterations. Methods This investigation was a double-blind, crossover design study of 15 young, healthy male participants who were allocated in random order to three oral treatments: placebo and 5-mg and 7.5-mg donepezil (doses which exert clinical and acute cognitive effects without considerable peripheral side effects). At the theoretical peak-plasma concentrations of donepezil, volunteers rated how they felt on validated questionnaires, which included various dimensions of subjective feelings. We also assessed changes in brain-derived neurotrophic factor (BDNF), which is increased by donepezil after chronic regimes and is related to modulation of mood. Results Donepezil significantly increased ratings of vigour and anxiety symptoms (medium effect sizes). No changes in bodily symptoms or BDNF were observed. Conclusions Acute donepezil administration in participants with unaltered cholinergic and dopaminergic tone led to positive and negative changes in affect. These results call for further research on the direct mood effects of donepezil. Copyright (c) 2013 John Wiley & Sons, Ltd.
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    Atypical antipsychotic drugs and tardive dyskinesia: relevance of D-2 receptor affinity
    (Sage Publications Ltd, 2004-03-01) Bressan, R. A.; Jones, H. M.; Pilowsky, L. S.; Universidade Federal de São Paulo (UNIFESP); Inst Psychiat
    Evidence suggests atypical antipsychotic treatment is associated with a Lower incidence of tardive dyskinesia (TD) than typical antipsychotic drugs, and is a potential antidyskinetic treatment. We present the case of a middle-aged woman never previously exposed to antipsychotic treatment who developed TD after 6 months of olanzapine monotherapy. Substitution of quetiapine for otanzapine alleviated her TD symptoms. the case demonstrates that atypical antipsychotic drugs have different effects in relation to TD. Potential psychopharmacological mechanisms explaining these differences are discussed, highlighting the importance of D-2 receptor occupancy by atypical antipsychotic drugs for TD.
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    Avaliação do efeito neuroprotetor da cafeína em modelo experimental de doença de parkinson: um estudo comportamental, neuroquímico e imunohistoquímico
    (Universidade Federal de São Paulo (UNIFESP), 2013-12-20) Machado Filho, Joao Ananias [UNIFESP]; Cavalheiro, Esper Abrao Cavalheiro [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The occurrence of clinical symptoms is related to the loss of approximately 80% of striatal dopamine and 50% of nigral neurons. Caffeine (CAF) is a methylxanthine with extensive use in medicines and products such as coffee, tea and chocolates, and being assigned neuroprotective activities. This study evaluated neuroprotective effects of caffeine in an animal model of PD induced by 6 - OHDA through behavioral studies, neurochemical and immunohistochemical studies. The animals, male Wistar rats (250-300g) were subjected to three protocols (P1, P2, P3) of striatal lesion by 6-OHDA, with concentration of 24μg/2μL in P1, and 12μg/2μL in P2 and P3. The preventive and curative treatment was done as follows in the these protocols: P1 - CAF treatment (10 and 20mg/kg) for two weeks after the injury (curative); P2 - CAF treatment (10 and 20mg/kg) for two weeks after the injury (curative); another group was treated with CAF (10 mg/kg) and L-Dopa (10mg/kg) after injury (curative); P3 - treated with CAF (5, 10 and 20mg/kg) for two weeks prior to the injury (prophylactic) and continued for two weeks after the injury (curative). The results demonstrate that the 6- OHDA caused an increase in the number of contralateral rotations induced by apomorphine and reduction of striatal dopamine levels with the degree of lesion probably directly related to the dose of 6-OHDA. These effects were reversed by the administration of CAF (10 and 20mg/kg) in P1 and P2, besides being observed increased neuronal viability and immunohystochemical changes that, together, denote neuroprotective activity of CAF in this model. Co-administration of levodopa (10 mg/kg) and CAF (10mg/kg) showed no effect on striatal dopamine concentrations beyond those already observed in the treatment with isolated CAF. CAF (20mg/kg) produced a significant increase in dopamine levels in sham animals and animals lesioned with 6-OHDA. Preventive treatment with caffeine (P3) showed similar results to curative treatment (P2) as observed in the neurochemical and behavioral assessments. Thus, it was demonstrated the neuroprotective effect of caffeine in this experimental study, presenting itself as a potential substance for the prevention and treatment of Parkinson's disease.
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    Behavioural and neurochemical effects of phosphatidylserine in MPTP lesion of the substantia nigra of rats
    (Elsevier B.V., 2004-01-26) Perry, J. C.; Da Cunha, C.; Anselmo-Franci, J.; Andreatini, R.; Miyoshi, E.; Tufik, Sergio [UNIFESP]; Vital, MABF; Univ Fed Parana; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    The present study investigated the effects of intranigral MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) infusion on rats treated with phosphatidylserine and evaluated in two memory tasks and on striatal dopamine levels. the results indicated that MPTP produced a significant decrease in the avoidance number in comparison to sham-operated and non-operated rats submitted to a two-way avoidance task. MPTP-lesioned rats exhibited an increase in the latencies to find the platform in cued version of the water maze in comparison to sham-operated and non-operated animals. the tested toxin reduced striatal dopamine levels in comparison to sham-operated and non-operated groups. A final surprising result was that phosphatidylserine was unable to reverse the cognitive deficits produced by MPTP or the reduction of striatal dopamine levels. in conclusion, the data suggest that MPTP is a good model to study the early impairment associated with Parkinson's disease and phosphatidylserine did not improve the memory impairment induced by MPTP. (C) 2003 Elsevier B.V. All rights reserved.
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    Blockage of dopaminergic D-2 receptors produces decrease of REM but not of slow wave sleep in rats after REM sleep deprivation
    (Elsevier B.V., 2008-04-09) Lima, Marcelo M. S. [UNIFESP]; Andersen, Monica L. [UNIFESP]; Reksidler, Angela B.; Silva, Andressa [UNIFESP]; Zager, Adriano [UNIFESP]; Zanata, Silvio M.; Vital, Maria A. B. E.; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Fed Parana
    Dopamine (DA) has, as of late, become singled out from the profusion of other neurotransmitters as what could be called a key substance, in the regulation of the sleep-wake states. We have hypothesized that dopaminergic D-2 receptor blockage induced by haloperidol could generate a reduction or even an ablation of rapid eye movement (REM) sleep. Otherwise, the use of the selective D-2 agonist, piribedil, could potentiate REM sleep. Electrophysiological findings demonstrate that D-2 blockage produced a dramatic reduction of REM sleep during the rebound (REB) period after 96 h of REM sleep deprivation (RSD). This reduction of REM sleep was accompanied by an increment in SWS, which is possibly accounted for the observed increase in the sleep efficiency. Conversely, our findings also demonstrate that the administration of piribedil did not generate additional increase of REM sleep. Additionally, D-2 receptors were found down-regulated, in the haloperidol group, after RSD, and subsequently up-regulated after REB group, contrasting to the D-1 down-regulation at the same period. in this sense, the current data indicate a participation of the D-2 receptor for REM sleep regulation and consequently in the REM sleep/SWS balance. Herein, we propose that the mechanism underlying the striatal D-2 up-regulation is due to an effect as consequence of RSD which originally produces selective D-2 supersensitivity, and after its period probably generates a surge in D-2 expression. in conclusion we report a particular action of the dopaminergic neurotransmission in REM sleep relying on D-2 activation. (c) 2007 Elsevier B.V. All rights reserved.
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    Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls
    (Assoc Brasileira Psiquiatria, 2017) Matsuzaka, Camila T. [UNIFESP]; Christofolini, Denise; Ota, Vanessa K. [UNIFESP]; Gadelha, Ary [UNIFESP]; Berberian, Arthur A. [UNIFESP]; Noto, Cristiano [UNIFESP]; Mazzotti, Diego R. [UNIFESP]; Spindola, Leticia M. [UNIFESP]; Moretti, Patricia N. [UNIFESP]; Smith, Marilia A. C. [UNIFESP]; Melaragno, Maria I. [UNIFESP]; Belangero, Sintia I. [UNIFESP]; Bressan, Rodrigo A. [UNIFESP]
    Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. Results: We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype* group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. Conclusion: These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.
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    Cellular prion protein is present in dopaminergic neurons and modulates the dopaminergic system
    (Wiley-Blackwell, 2014-08-01) Rial, Daniel; Pamplona, Fabricio A.; Moreira, Eduardo L. G.; Moreira, Karin M. [UNIFESP]; Hipolide, Debora [UNIFESP]; Rodrigues, Diana I.; Dombrowski, Patricia A.; Da Cunha, Claudio; Agostinho, Paula; Takahashi, Reinaldo N.; Walz, Roger; Cunha, Rodrigo A.; Prediger, Rui D.; Universidade Federal de Santa Catarina (UFSC); Rua Larga Univ Coimbra; DOr Inst Res & Educ; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do Paraná (UFPR); Univ Coimbra; Hosp Governador Celso Ramos
    Cellular prion protein (PrPC) is widely expressed in the brain. Although the precise role of PrPC remains uncertain, it has been proposed to be a pivotal modulator of neuroplasticity events by regulating the glutamatergic and serotonergic systems. Here we report the existence of neurochemical and functional interactions between PrPC and the dopaminergic system. PrPC was found to co-localize with dopaminergic neurons and in dopaminergic synapses in the striatum. Furthermore, the genetic deletion of PrPC down-regulated dopamine D-1 receptors and DARPP-32 density in the striatum and decreased dopamine levels in the prefrontal cortex of mice. This indicates that PrPC affects the homeostasis of the dopaminergic system by interfering differently in different brain areas with dopamine synthesis, content, receptor density and signaling pathways. This interaction between PrPC and the dopaminergic system prompts the hypotheses that the dopaminergic system may be implicated in some pathological features of prion-related diseases and, conversely, that PrPC may play a role in dopamine-associated brain disorders.
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    Dopamine induces the accumulation of insoluble prion protein and affects autophagic flux
    (Frontiers Research Foundation, 2015-02-02) Luz, Marcio Henrique Mello da [UNIFESP]; Peres, Italo T. [UNIFESP]; Santos, Tiago G.; Martins, Vilma R.; Icimoto, Marcelo Yudi [UNIFESP]; Lee, Kil Sun [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Metodista São Paulo; AC Camargo Canc Ctr
    Accumulation of protein aggregates is a histopathological hallmark of several neurodegenerative diseases, but in most cases the aggregation occurs without defined mutations or clinical histories, suggesting that certain endogenous metabolites can promote aggregation of specific proteins. One example that supports this hypothesis is dopamine and its metabolites. Dopamine metabolism generates several oxidative metabolites that induce aggregation of alpha-synuclein, and represents the main etiology of Parkinson's diseases. Because dopamine and its metabolites are unstable and can be highly reactive, we investigated whether these molecules can also affect other proteins that are prone to aggregate, such as cellular prion protein (PrPC). in this study, we showed that dopamine treatment of neuronal cells reduced the number of viable cells and increased the production of reactive oxygen species (ROS) as demonstrated in previous studies. Overall PrPC expression level was not altered by dopamine treatment, but its unglycosylated form was consistently reduced at 100 mu M of dopamine. At the same concentration, the level of phosphorylated mTOR and 4EBP1 was also reduced. Moreover, dopamine treatment decreased the solubility of PrPC, and increased its accumulation in autophagosomal compartments with concomitant induction of LC3-II and p62/SQSTM1 levels. in vitro oxidation of dopamine promoted formation of high-order oligomers of recombinant prion protein. These results suggest that dopamine metabolites alter the conformation of PrPC, which in turn is sorted to degradation pathway, causing autophagosome overload and attenuation of protein synthesis. Accumulation of PrPC aggregates is an important feature of prion diseases. Thus, this study brings new insight into the dopamine metabolism as a source of endogenous metabolites capable of altering PrPC solubility and its subcellular localization.
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    Dopamine Transporter Regulation during Four Nights of REM Sleep Deprivation Followed by Recovery - An in vivo Molecular Imaging Study in Humans
    (Amer Acad Sleep Medicine, 2010-02-01) Martins, R. C. S. [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Garbuio, Silvério Aparecido [UNIFESP]; Bittencourt, Lia Rita Azeredo [UNIFESP]; Guindalini, Camila [UNIFESP]; Shih, M. C. [UNIFESP]; Hoexter, M. Q. [UNIFESP]; Bressan, Rodrigo Affonseca. A. [UNIFESP]; Castiglioni, M. L. V. [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objectives: To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers.Design: Prospective study.Setting: Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [(99m)Tc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity.Patients or Participants: Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived).Measurements and Results: Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation.Conclusion: Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.
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    Effects of acute and long-term typical or atypical neuroleptics on morphine-induced behavioural effects in mice
    (Wiley-Blackwell, 2014-03-01) Hollais, Andre W. [UNIFESP]; Patti, Camilla L. [UNIFESP]; Zanin, Karina A. [UNIFESP]; Fukushiro, Daniela F. [UNIFESP]; Berro, Lais F. [UNIFESP]; Carvalho, Rita C. [UNIFESP]; Kameda, Sonia R. [UNIFESP]; Frussa-Filho, Roberto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    It has been suggested that the high prevalence of drug abuse in schizophrenics is related to chronic treatment with typical neuroleptics and dopaminergic supersensitivity that develops as a consequence. Within this context, atypical neuroleptics do not seem to induce this phenomenon. in the present study, we investigated the effects of acute administration or withdrawal from long-term administration of haloperidol and/or ziprasidone on morphine-induced open-field behaviour in mice. in the first experiment, mice were given a single injection of haloperidol (1mg/kg, i.p.) or several doses of ziprasidone (2, 4 or 6mg/kg, i.p.) and motor activity was quantified by the open-field test. the aim of the second experiment was to verify the effects of an acute injection of haloperidol (1mg/kg) or ziprasidone (6mg/kg) on 20mg/kg morphine-induced behaviours in the open-field test. in the third experiment, mice were treated with 1mg/kg haloperidol and/or 2, 4 or 6mg/kg ziprasidone for 20days. Seventy-two hours after the last injection, mice were injected with 20mg/kg, i.p., morphine and then subjected to the open-field test. Acute haloperidol or ziprasidone decreased spontaneous general activity and abolished morphine-induced locomotor stimulation. Withdrawal from haloperidol or ziprasidone did not modify morphine-elicited behaviours in the open-field test. the results suggest that withdrawal from neuroleptic treatments does not contribute to the acute effect of morphine in schizophrenic patients.
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    Effects of buspirone on an animal model of tardive dyskinesia
    (Elsevier B.V., 1999-11-01) Queiroz, Claudio MT [UNIFESP]; Frussa-Filho, Roberto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    1. the effects of buspirone were studied on an animal model of tardive dyskinesia, i.e., the quantification of orofacial dyskinesia in rats repeatedly treated with reserpine.2. Rats were co-treated with saline [SAL] or buspirone [BUS] (3.0 mg/kg, i.p., twice daily) and vehicle [VEH] or reserpine [RES] (0.1 mg/kg, s.c., once every other day) for 19 days. On the day 20, the animals were observed for quantification of the behavioral parameters of orofacial dyskinesia: tongue protrusion and vacuous chewing movements frequencies and duration of twitching of the facial musculature.3. Rats of the SAL+RES group exhibited a significant increase in the three behavioral parameters of orofacial dyskinesia relative to the rats of the SAL+VEH group. However, animals of the BUS+RES group showed only an increased frequency of vacuous chewing movements when compared to animals of the SAL+VEH group. in addition, the duration of the facial twitching was significantly decreased in the BUS+RES group in relation to rats of the SAL+RES group. There were no significant differences in the orofacial parameters between the BUS+VEH and the SAL+VEH groups.4. Because it was also verified that chronic buspirone treatment was able to increase apomorphine-induced yawning behavior, the possibility is raised that buspirone attenuates reserpine-induced orofacial dyskinesia through the development of dopamine autoreceptor supersensitivity.
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    Effects of continuous exposure to light on behavioral dopaminergic supersensitivity
    (Elsevier B.V., 1999-06-15) Abilio, V. C.; Freitas, F. M.; Dolnikoff, M. S.; Castrucci, AML; Frussa, R.; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Background: This study examines the effects of long-term continuous exposure to light on dopaminergic supersensitivity induced by repented treatment with haloperidol in rats,Methods: Spontaneous general activity in an open-field (SGA) and stereotyped behavior induced by apomorphine (SB-APO) or amphetamine (SB-AMP) were used as experimental parameters. Rats were allocated to four groups in each experiment: saline-treated animals kept under a 12-hour light/dark cycle (LD) or 24-hour light/light cycle (LL), and 2 mg/kg haloperidol-treated animals kept under the above cycles. Plasma corticosterone concentration was also measured by radioimunoassay in saline-treated mts kept under a LD or LL cycle.Results: All the behavioral parameters used showed the development of central dopaminergic supersensitivity in rats kept under both cycles. Continuous exposure to light enhanced SGA and SB-AMP in both saline- and haloperidol-treated mts, but did not modify SB-APO. Animals kept under the LL cycle presented an increased plasma corticosterone concentration.Conclusions: Our results suggest that continuous exposure to light leads to an increase in dopaminergic function in both normal and supersensitive rats. This effect seems to be mediated by a presynaptic mechanism possibly involving corticosterone actions. (C) 1999 Society of Biological Psychiatry.
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    Effects of haloperidol and GM(1) ganglioside treatment on striatal D-2 receptor binding and dopamine turnover
    (Elsevier B.V., 1998-02-20) Vital, MABF; Florio, J. C.; Frussa, R.; De Lucia, R.; Tufik, S.; Palermo-Neto, J.; Universidade de São Paulo (USP); Univ Fed Parana; Universidade Federal de São Paulo (UNIFESP)
    Previous studies have shown that whereas exogenous GM(1) ganglioside co-administration leads to an increase of haloperidol-induced behavioral supersensitivity, GM(1) significantly attenuates the behavioral parameters of dopaminergic supersensitivity when administered after abrupt haloperidol withdrawal. in the present study, the effects of GM(1) and haloperidol co-administration (5 mg/kg GM(1) i.p. and 1 mg/kg haloperidol i.p., twice daily, for 30 days) as well as the effects of a 3 day treatment with GM(1) were investigated in rats withdrawn from haloperidol administration by measuring striatal D-2 dopamine receptor binding and dopamine turnover. the results showed that under these two experimental conditions GM(1) modified neither the haloperidol-induced striatal D-2 dopamine receptor up regulation nor the decrease in dopamine turnover produced by haloperidol withdrawal These results suggest that the effects of GM(1) on behavioral supersensitivity are not related to modifications in dopamine receptor number or affinity and in the synaptic availability of this catecholamine.
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    Effects of melatonin on behavioral dopaminergic supersensitivity
    (Elsevier B.V., 2003-05-16) Abilio, V. C.; Vera, JAR; Ferreira, LSM; Duarte, CRM; Martins, C. R.; Torres-Leite, D.; Ribeiro, R. D.; Frussa, R.; Universidade Federal de São Paulo (UNIFESP)
    This study examines the effects of melatonin on dopaminergic supersensitivity induced by long-term treatment with haloperidol in rats. Enhancements of spontaneous general activity in an open-field and of stereotyped behavior induced by apomorphine after abrupt withdrawal from long-term treatment with haloperidol were used as experimental parameters for dopaminergic supersensitivity. Experiment 1 was conducted to investigate the effects of melatonin on the development of dopaminergic supersensitivity, and experiment 2 was conducted to investigate the effects of melatonin on the development as well as on expression of dopaminergic supersensitivity. Rats of both experiments were long-term treated with saline or haloperidol concomitant to saline or melatonin. in experiment 1 behavioral observations were performed after abrupt withdrawal from long-term treatment. in experiment 2 behavioral observations were performed 1 hour after an acute injection of saline or melatonin, administered after the abrupt withdrawal from long-term treatment. Both behavioral parameters used showed the development of central dopaminergic supersensitivity in rats treated with haloperidol since 24 hours after abrupt withdrawal. Concomitant treatment with melatonin intensified haloperidol-induced dopaminergic supersensitivity, observed 72 hours after withdrawal. Melatonin treatment per se also induced behavioral supersensitivity evaluated by both open-field and stereotyped behaviors, although it was more fugacious than that presented by haloperidol. Acute treatment with melatonin reverted the enhancement of the haloperidol-induced dopaminergic supersensitivity produced by concomitant long-term treatment with melatonin, as well as melatonin-induced dopaminergic supersensitivity per se. Our results support previous evidence of antidopaminergic effects of melatonin and demonstrate that repeated administration of this hormone modifies the plasticity of behaviors mediated by central dopaminergic systems. (C) 2003 Elsevier Science Inc. All rights reserved.
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    Effects of Sulpiride on True and False Memories of Thematically Related Pictures and Associated Words in Healthy Volunteers
    (Frontiers Media Sa, 2016) Guarnieri, Regina V. [UNIFESP]; Ribeiro, Rafaela L. [UNIFESP]; Lino de Souza, Altay A.; Galduroz, Jose Carlos F. [UNIFESP]; Covolan, Luciene [UNIFESP]; Bueno, Orlando F. A. [UNIFESP]
    Episodic memory, working memory, emotional memory, and attention are subject to dopaminergic modulation. However, the potential role of dopamine on the generation of false memories is unknown. This study defined the role of the dopamine D-2 receptor on true and false recognition memories. Twenty-four young, healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a dopamine D-2-receptor antagonist, just before starting the recognition memory task in a randomized, double-blind, and placebo-controlled trial. The sulpiride group presented more false recognitions during visual and verbal processing than the placebo group, although both groups had the same indices of true memory. These findings demonstrate that dopamine D-2 receptors blockade in healthy volunteers can specifically increase the rate of false recognitions. The findings fit well the two-process view of causes of false memories, the activation/monitoring failures model.
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    Haloperidol increases false recognition memory of thematically related pictures in healthy volunteers
    (Wiley, 2017) Guarnieri, Regina Vieira [UNIFESP; Buratto, Luciano G.; Gomes, Carlos F. A.; Ribeiro, Rafaela Larsen [UNIFESP]; Souza, Altay Alves Lino de [UNIFESP]; Stein, Lilian M.; Galduróz, José Carlos Fernandes [UNIFESP]; Bueno, Orlando Francisco Amodeo [UNIFESP]
    Dopamine can modulate long-term episodic memory. Its potential role on the generation of false memories, however, is less well known. In a randomized, double-blind, placebo-controlled experiment, 24 young healthy volunteers ingested a 4-mg oral dose of haloperidol, a dopamine D-2-receptor antagonist, or placebo, before taking part in a recognition memory task. Haloperidol was active during both study and test phases of the experiment. Participants in the haloperidol group produced more false recognition responses than those in the placebo group, despite similar levels of correct recognition. These findings show that dopamine blockade in healthy volunteers can specifically increase false recognition memory.
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    Hemiparkinsonian rats rotate toward the side with the weaker dopaminergic neurotransmission
    (Elsevier B.V., 2008-06-03) Da Cunha, Claudio; Wietzikoski, Evellyn Claudia; Ferro, Marcelo Machado; Martinez, Glaucia Regina; Barbato Frazao Vital, Maria Aparecida; Hipolide, Debora [UNIFESP]; Tufik, Sergio [UNIFESP]; Canteras, Newton Sabino; Universidade Federal do Paraná (UFPR); Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Rats with unilateral lesion of the substantia nigra pars compacta (SNpc) have been used as a model of Parkinson's disease. Depending on the lesion protocol and on the drug challenge, these rats rotate in opposite directions. the aim of the present study was to propose a model to explain how critical factors determine the direction of these turns. Unilateral lesion of the SNpc was induced with 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Separate analysis showed that neither the type of neurotoxin nor the site of lesion along the nigrostriatal. pathway was able to predict the direction of the turns these rats made after they were challenged with apomorphine. However, the combination of these two factors determined the magnitude of the lesion estimated by tyrosine-hydroxylase immunohistochemistry and HPLC-ED measurement of striatal dopamine. Very small lesions did Dot cause turns, medium-size lesions caused ipsiversive turns, and large lesions caused contraversive turns. Large-size SNpc lesions resulted in an increased binding of [H-3] raclopride to D2 receptors, while medium-size lesions reduced the binding of [H-3]SCH-23390 D1 receptors in the ipsilateral striatum. These results are coherent with the model proposing that after challenged with a dopamine receptor agonist, unilaterally SNpc-lesioned rats rotate toward the side with the weaker activation of dopamine receptors. This activation is weaker on the lesioned side in animals with small SNpc lesions due to the loss of dopamine, but stronger in animals with large lesions due to dopamine receptor supersensitivity. (C) 2008 Elsevier B.V. All rights reserved.
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    Increased brain dopamine D4-like binding after chronic ethanol is not associated with behavioral sensitization in mice
    (Elsevier B.V., 2005-10-01) Quadros, IMH; Nobrega, J. N.; Hipolide, D. C.; Souza-Formigoni, MLO; Universidade Federal de São Paulo (UNIFESP); Ctr Addict & Mental Hlth
    Dopaminergic D4 receptors have been hypothesized to be involved in neuropsychiatric disorders and substance abuse. in mice. repeated ethanol administration may induce behavioral sensitization, a phenomenon of increased sensitivity to the drug's stimulant properties. This study aimed to analyze brain D4 receptors binding in mice with different levels of behavioral sensitization to ethanol. Male Swiss mice received 2.2 g/kg ethanol (n = 64) or saline (n = 16) intraperitoneally daily for 21 days and were weekly tested for locomotor activity and for blood ethanol levels. According to the locomotor scores presented across test days, ethanol-treated mice were classified as sensitized or nonsensitized. Twenty-four hours after the last administration, mice were sacrificed and brains were processed for autoradiography. Brain D4 binding was assessed by quantitative autoradiography using [H-3]nemonapride + raclopride in three groups: saline-treated controls (n = 10), ethanol-sensitized (n = 11), and ethanol-nonsensitized (n = 9) mice. Both sensitized and nonsensitized mice showed higher D4 binding densities than saline-treated controls in the posterior caudate-putamen and the olfactory tubercle (p < .02), but only sensitized mice presented higher D4 binding than controls at the lateral septal nucleus (p < .02). However, there were no differences between sensitized and nonsensitized mice in any of the brain regions analyzed. Furthermore, sensitized and nonsensitized mice presented similar blood ethanol levels during the treatment. the higher D4 binding levels observed in both ethanol-treated subgroups (sensitized and nonsensitized) suggest that chronic ethanol treatment may induce upregulation of D4 receptors in specific brain regions. However, this mechanism does not seem to be associated with the differential ability to develop behavioral sensitization to ethanol in mice. (c) 2005 Elsevier Inc. All rights reserved.
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    Influence of Chronic Dopamine Transporter Inhibition by RTI-336 on Motor Behavior, Sleep, and Hormone Levels in Rhesus Monkeys
    (Amer Psychological Assoc, 2012-04-01) Andersen, Monica L. [UNIFESP]; Carroll, F. Ivy; Sawyer, Eileen K.; Howell, Leonard L.; Emory Univ; Universidade Federal de São Paulo (UNIFESP)
    Dopamine transporter (DAT) inhibitors have been developed as a promising treatment approach for cocaine dependence. However, the stimulant effects of DAT inhibitors have the potential to disrupt sleep patterns, and the influence of long-term treatment on dopamine neurochemistry is still unknown. the objectives of this study were to (1) explore the stimulant-related effects of chronic DAT inhibitor (RTI-336) treatment on motor activity and sleep-like measures in male rhesus monkeys (Macaca mulatta; n = 4) and (2) to determine the effect of drug treatment on prolactin and cortisol levels. Subjects were fitted with a collar-mounted activity monitor to evaluate their motor activity, with 4 days of baseline recording preceding 21 days of daily saline or RTI-336 (1 mg/kg/day; intramuscular) injections. Blood samples were collected immediately prior to and following chronic treatment to assess hormone levels. RTI-336 produced a significant increase in locomotor activity at the end of the daytime period compared to saline administration. During the 3-week treatment period, sleep efficiency was decreased and the fragmentation index and latency to sleep onset were significantly increased. Hormone levels were not changed throughout the study. Chronic treatment with RTI-336 has a mild but significant stimulant effect, as evidenced by the significant increase in activity during the evening period which may cause minor disruptions in sleep measures.
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    Intra-nigral MPTP lesion in rats: Behavioral and autoradiography studies
    (Elsevier B.V., 2005-10-01) Perry, J. C.; Hipolide, D. C.; Tufik, S.; Martins, R. D.; Da Cunha, C.; Andreatini, R.; Vital, MABF; Univ Fed Parana; Universidade Federal de São Paulo (UNIFESP)
    The present study investigated the motor response and possible changes in binding to D-1 and D-2 receptors after intra-nigral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion on rats. the results indicated that MPTP-lesioned rats exhibited a significant reduction in locomotion and rearing frequencies observed in an open field 24 h after surgery. However, at 7 and 14 days after surgery the MPTP-lesioned rats showed a significant increase in locomotion in comparison to the control groups, as well as a decrease in immobility time. in addition, 21 days after surgery the behavioral measurements were unaltered by these procedures. Moreover, latency in initiating movement and catalepsy were unchanged by this neurotoxin on the same days of observation. An autoradiography approach indicated that there was a reduction in [H-3]SCH 23390 binding in substantia nigra pars compacta (SNpc), substantia nigra pars reticulata (SNpr) and ventrolateral striatum in MPTP-treated rats 21 days after the surgery. [H-3]raclopride binding remained unaltered by the MPTP treatment. These results suggest that compensatory plastic changes occur in D I dopamine receptors after partial lesion of nigral dopaminergic neurons. These alterations might be related to the occurrence and recovery of motor impairment observed in MPTP-lesioned rats. (c) 2005 Elsevier Inc. All rights reserved.