The influence of cerebral 5-hydroxytryptamine on catalepsy induced by brain-amine depleting neuroleptics or by cholinomimetics.

1 Catalepsy was produced in rats and mice by the subcutaneous injection of either tetrabenazine or the butyrophenone U-32,802A (4'-fluoro-4-{[4-(p-fluorophenyl)-3-cyclohexen-1-yl]amino} butyrophenone hydrochloride). Catalepsy was evaluated by the duration of total immobility on a vertical grid.2 Pretreatment with p-chlorophenylalanine (PCPA) reduced the intensity of catalepsy by 50% or more, whereas its time course remained the same.3 5-Hydroxytryptophan (5-HTP), 10 mg/kg, enhanced the catalepsy induced by U-32,802A or tetrabenazine, provided it was administered soon (45 min) after the neuroleptic; injections at 90 min had no effect. Otherwise untreated rats given this dose of 5-HTP behaved normally on the grid.4 The anticataleptic effect of PCPA was reversed by 5-HTP.5 Measurable changes in 5-hydroxytryptamine (5-HT) metabolism in the rat forebrain accompanied the modification of catalepsy by 5-HTP and PCPA.6 Methysergide (5 mg/kg) given 30 min before the neuroleptics to either mice or rats reduced the catalepsy, assessed 2.5 h after the methysergide. It also prevented the increase in neuroleptic-induced catalepsy following 5-HTP, 10 mg/kg.7 Tryptophan, like 5-HTP, increased the catalepsy seen in mice after U-32,802A and tetrabenazine, and increased the production of 5-hydroxyindol-3-ylacetic acid in the forebrain.8 In the rat, intracerebroventricular injection of physostigmine produced catalepsy which was not modified by methysergide or PCPA but was abolished by atropine. Similarly, in the mouse, catalepsy induced by the subcutaneous injection of pilocarpine was abolished by atropine but not affected by either methysergide or 5-HTP.9 Atropine greatly reduced the catalepsy induced by U-32,802A and tetrabenazine but lowered striatal homovanillic acid (HVA) only after U-32,802A. D,L-DOPA, 20 mg/kg, diminished the cataleptogenic effect of both neuroleptics and raised striatal HVA.10 The results support the view that there is a facilitating or permissive action of 5-HT-containing neurones on neuroleptic-induced catalepsy.