Neuropharmacological and behavioral evaluation of prostaglandin E2 and 11-thiol-11-desoxy prostaglandin E2 in the mouse and rat.
Prostaglandin E2 (PGE2) and 11-thiol-11-desoxy Prostaglandin E2 (SHPGE2) were evaluated in a variety of behavioral and neuropharmacological procedures that are sensitive to neuroleptics. Clozapine (C), thioridazine (T), haloperidol (H), and fluphenazine (F) were also tested for comparison. All agents except T suppressed avoidance responses in trained rats at one or more doses without concurrently disrupting escape behavior. T, H, and F dose-responsively antagonized lesioned rat rotational behavior at nontoxic doses. T, H, and F induced catalepsy at doses considerably higher than those effective on rotational behavior. SHPGE2, PGE2, and C did not cause catalepsy and did not show statistically significant dose-response antagonism of rotational behavior at less than toxic doses. All agents tested blocked d-amphetamine-induced lethality and caused motor incoordination dose-responsively. SHPGE2, PGE2, C, and T caused statistically significant blockade of physostigmine-induced lethality. H and F were ineffective against physostigmine lethality. It was concluded that SHPGE2 and PGE2 demonstrated, qualitatively, a spectrum of neuroleptic like properties remarkably similar to C.
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced; D003024:Clozapine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D005476:Fluphenazine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010830:Physostigmine / Q000037:antagonists & inhibitors / Q000633:toxicity; D011458:Prostaglandins E / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects; D013881:Thioridazine / Q000494:pharmacology
D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D010830:Physostigmine; D003024:Clozapine; D006220:Haloperidol; D013881:Thioridazine; D005476:Fluphenazine; D003913:Dextroamphetamine