Psychotomimetics moderately affect dopamine receptor binding in the rat brain

The hypothesis that psychotomimetics induce a rapid dopamine receptor regul ation that could participate in the expression of the brain dopaminergic ov eractivation and in the early signs of psychotic-like behaviour, was checke d by radioligand binding on rat brain cryosections. For this purpose, subch ronic 7-day-d-amphetamine pretreatment was combined with acute amphetamine, phencyclidine or LSD challenge. Acute application of psychotomimetics affe cted only striatal and accumbens but not nigral and olfactory dopamine rece ptor binding after 40 min, while subchronic amphetamine expressed no effect , as revealed by two-way ANOVA. Post-hoc statistical analysis showed that o nly striatal and accumbens[H-3]SCH 23390 binding decrease (10-12%) followin g phencyclidine and striatal [H-3]spiperone binding increase (11%) after ac ute amphetamine were significant. It is assumed that such moderate dopamine receptor binding changes probably reflect the fast receptor regulation res ponses without important influence on a proposed drug-induced dopaminergic overactivity. The registered alterations of D-1 receptor binding after phen cyclidine are suggested to be capable to modify the activity of some other neural pathways in the basal ganglia and thus participate in a psychotic-li ke behaviour. (C) 2000 Elsevier Science Ltd. All rights reserved.