Behavioural effects of serotonin agonists and antagonists in the rat and marmoset

The present study was conducted to investigate the effects of various 5-hydroxytryptamine (5-HT) agonists and antagonists on motor behaviour in rats and marmosets. Various motor-based responses were assessed after central or peripheral administration of 5-HT agents to rats and marmosets. Drugs acting as agonists at the 5-HT1A receptor (8-OHDPAT, gepirone, BMY-7378, NAN-190, PAPP (LY165163) and flesinoxan) and 5-HT2/1C receptors (DOI) were found to reverse neuroleptic-induced catalepsy in the rat whereas 5-HT2/1C antagonists (mianserin, ritanserin and ICI-170,809) and the 5-HT1 antagonist ((+/-)pindolol) increased catalepsy. Agonists acting at 5-HT3 receptors (phenylbiguanide and 2-methyl-5-HT) had no effect on catalepsy. The putative 5-HT1A antagonist, (+/-) pindolol, attenuated the reversal of catalepsy by 8-OHDPAT. Although both 8-OHDPAT and BMY-7378 were tested, only the latter was found to reduce apomorphine-induced stereotypy. Bilateral or unilateral infusions of 8-OHDPAT, BMY-7378 or pindolol into the substantia nigra of non-lesioned rats had no effect on spontaneous locomotor or rotational activity, respectively. However, 8-OHDPAT and BMY-7378 were found to increase or decrease motor activity, after injection into the median or dorsal raphe nuclei, respectively. Finally, 8-OHDPAT and BMY-7378 were found to be inactive against MPTP-induced bradykinesia in the marmoset. It is concluded that both 5-HT1A and 5-HT2/1C receptors are involved in the anti-cataleptic effects of 5-HT agents. The 5-HT1A receptors are probably situated within the raphe, whereas the location of the 5-HT2/1C receptors remains undetermined.