Effects of dopaminergic and cholinergic drugs. naloxone and l-prolyl-leucyl-glycinamide on LSD-induced catalepsy.
In an attempt to elucidate the mechanism of d-lysergic acid diethylamide (LSD) induced catalepsy, the effects of cholinergic and dopaminergic agents, naloxone and L-propyl-leucyl-glycinamide (PLG) were studied in rats. The dose-dependent (50--500 micrograms kg-1 s.c.) and time-related cataleptic response elicited by LSD was preceded by a phase of hyperexcitability. The non-hallucinogenic analogue, 2-bromo-LSD (BOL), was without effect. Both apomorphine, the dopamine agonist, and L-DOPA antagonized LSD-induced catalepsy whereas the dopamine depleting agent alpha-methyl-p-tyrosine (alpha-MPT) slightly prolonged the cataleptic effect. Cholinergic muscarinic receptor stimulation with pilocarpine antagonized LSD-induced catalepsy. The muscarinic antagonists, atropine and scopolamine, intensified the hyperexcitable phase and potentiated the cataleptic effects of LSD. Nicotine slightly potentiated LSD action but mecamylamine antagonized it. While pre-treatment with naloxone, the narcotic antagonist and PLG prolonged the cataleptic response, post-treatment with naloxone effectively attenuated LSD-induced catalepsy. The behavioural data are interpreted to suggest that LSD-induced catalepsy may be mediated through diminished dopaminergic and cholinergic neuronal activity and under enkephalinergic modulation. The neuroanatomical foci and exact mechanism of action remain to be delineated.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009075:MSH Release-Inhibiting Hormone / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
D010277:Parasympathomimetics; D009270:Naloxone; D007980:Levodopa; D008238:Lysergic Acid Diethylamide; D009075:MSH Release-Inhibiting Hormone; D001058:Apomorphine