Participation of serotoninergic, GABA-ergic and opiate mechanisms in the genesis of amphetamine stereotypy.
In experiments on rats it has been observed that the intensity of amphetamine-induced (6 mg/kg s.c.) stereotypy is reduced by the blockers of the serotonin (5-HT), GABA- and opiate receptors, respectively danitracene (3 mg/kg i.p.), picrotoxin (2 mg/kg i.p.) and naloxone (10 mg/kg s.c.). Applied 24 hours after the serotonin depletor para-chlorophenylalanine (PCPA--300 mg/kg i.p.), amphetamine induced more pronounced but earlier disappearing stereotypy. Also more intensive but longer was the stereotypy induced by apomorphine (2.5 mg/kg i.p.) applied after PCPA. The stimulator of the serotonin receptors quipazine (10 mg/kg i.p.) potentiated amphetamine stereotypy and eliminated haloperidol catalepsy (1 mg/kg i.p.). The blocker of the cholinergic receptors atropine (30 mg/kg i.p.) increased and prolonged amphetamine stereotypy. In the interpretation of the results obtained an attempt is made to substantiate the thesis that dopamine (DA) released under the effect of amphetamine by the nigrostriatal terminals, acts at least partially not as inhibitory, as it is usually accepted, but as excitatory transmitter. It is considered that the results obtained show that DA released from the nigrostriatal pathway exercises its typical inhibitory influence on the striatum, by stimulating 5-HT, GABA and opiate neurons situated in nucleus caudatus. The ostensibly contradictory results from the experiments with PCPA to the proposed hypothesis are explained with the development of sensitization of the 5-HT receptors.
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004723:Endorphins / Q000502:physiology*; D010134:Fenclonine / Q000494:pharmacology; D006801:Humans; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D004723:Endorphins; D012701:Serotonin; D009270:Naloxone; D011814:Quipazine; D005680:gamma-Aminobutyric Acid; D001285:Atropine; D000661:Amphetamine; D001058:Apomorphine; D010134:Fenclonine