Psychotomimetics moderately affect dopamine receptor binding in the rat brain.
The hypothesis that psychotomimetics induce a rapid dopamine receptor regulation that could participate in the expression of the brain dopaminergic overactivation and in the early signs of psychotic-like behaviour, was checked by radioligand binding on rat brain cryosections. For this purpose, subchronic 7-day-d-amphetamine pretreatment was combined with acute amphetamine, phencyclidine or LSD challenge. Acute application of psychotomimetics affected only striatal and accumbens but not nigral and olfactory dopamine receptor binding after 40 min, while subchronic amphetamine expressed no effect, as revealed by two-way ANOVA. Post-hoc statistical analysis showed that only striatal and accumbens[3H]SCH 23390 binding decrease (10-12%) following phencyclidine and striatal [3H]spiperone binding increase (11%) after acute amphetamine were significant. It is assumed that such moderate dopamine receptor binding changes probably reflect the fast receptor regulation responses without important influence on a proposed drug-induced dopaminergic overactivity. The registered alterations of D1 receptor binding after phencyclidine are suggested to be capable to modify the activity of some other neural pathways in the basal ganglia and thus participate in a psychotic-like behaviour.
Tomić
M
M
Department of Biochemistry, Institute for Biological Research, Belgrade, Yugoslavia. mitomic@ibiss.bg.ac.yu
Joksimović
J
J
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D014316:Tritium
D001552:Benzazepines; D000697:Central Nervous System Stimulants; D006213:Hallucinogens; D011954:Receptors, Dopamine; D014316:Tritium; D013134:Spiperone; D008238:Lysergic Acid Diethylamide; D000661:Amphetamine; D010622:Phencyclidine; D003913:Dextroamphetamine