NEUROPHARMACOLOGICAL AND BEHAVIORAL EVALUATION OF PROSTAGLANDIN-E2 AND 11-THIOL-11-DESOXY PROSTAGLANDIN-E2 IN 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-responsive antagonism of rotational behavior at less than toxic doses. All agents tested blocked d-amphetamine-induced lethality and caused motor incoordination doseresponsively. 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 neurolepticlike properties remarkably similar to C. © 1978 Springer-Verlag.