Sensitization to ethanol's stimulant effect is associated with region-specific increases in brain D2 receptor binding

Sensitization to ethanol's stimulant effect is associated with region-specific increases in brain D2 receptor binding

Author Souza-Formigoni, MLO Google Scholar
De Lucca, E. M. Google Scholar
Hipolide, D. C. Google Scholar
Enns, S. C. Google Scholar
Oliveira, MGM Google Scholar
Nobrega, J. N. Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Ctr Addict & Mental Hlth
Abstract Rationale: Stimulation of locomotor activity by low doses of ethanol (EtOH) and the potentiation of this response after repeated administration (sensitization) have been related to EtOH's rewarding and addictive properties and to altered dopaminergic activity in brain. in mice, behavioral sensitization to EtOH occurs only in a subset of treated animals, and this provides an opportunity for distinguishing general drug effects from sensitization-specific brain effects. Objectives: in view of evidence suggesting a role for dopamine D2 receptors in EtOH preference and abuse liability, the present study addressed the hypothesis that D2 binding would be altered in specific brain regions in mice showing differential sensitization responses to chronic EtOH administration. Methods: Male albino Swiss mice received 2.4 g/kg EtOH i.p. daily for 21 days and were then separated into sensitized or non-sensitized subgroups on the basis of weekly locomotor activity tests. Results: Autoradiographic analyses of [H-3]raclopride binding to D2 sites revealed significant increases in the anterior caudate-putamen of mice in the EtOH-sensitized group when compared with either saline controls (+40%, P<0.00009) or to mice in the EtOH non-sensitized group (+32%; P<0.0003). Smaller increases were seen in the ventrolateral caudate-putamen of sensitized animals (+18% vs control, P<0.02; and 12% vs non-sensitized mice, P<0.07). No differences were found in other brain regions, including the nucleus accumbens, olfactory bulb and substantia nigra. Conclusions: the observed increases in D2-receptor binding in circumscribed targets of nigrostriatal projections may reflect either a pre-existing condition in sensitization-prone animals or a selective vulnerability of D2 receptors to chronic EtOH in these animals. in either case, it may be a marker for differential susceptibility to EtOH sensitization.
Keywords [H-3] raclopride
locomotor activity
Language English
Date 1999-10-01
Published in Psychopharmacology. New York: Springer Verlag, v. 146, n. 3, p. 262-267, 1999.
ISSN 0033-3158 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 262-267
Access rights Closed access
Type Article
Web of Science ID WOS:000083098400004

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