PHARMACOLOGICAL ACTION OF ZOTEPINE AND OTHER ANTIPSYCHOTICS ON CENTRAL 5-HYDROXYTRYPTAMINE RECEPTOR SUBTYPES

The effect of the atypical neuroleptic zotepine (CAS 26615-21-4), in c omparison with clozapine, risperidone and haloperidol, on the responsi veness of different 5-hydroxytryptamine (5-HT1) receptor subtypes to t heir agonists was examined in rats and mice. The above antipsychotics were investigated in the following behavioural tests: 8-OH-DPAT (8-hyd roxy-dipropylaminotetralin)- induced behavioural syndrome in rats, mCP P (m- chlorophenylpiperazine)-induced hypothermia in mice and mCPP-ind uced hypoactivity measured in the open field in rats. Zotepine, clozap ine and haloperidol did not affect the behavioural syndrome induced by 8-OH-DPAT (the selective agonist of 5-HT1A, receptor), only risperido ne (used in higher doses) attenuated the effect of 8-OH-DPAT. The mCPP -induced hypothermia in mice (a 5-HT1B effect) was affected by neither zotepine nor clozapine, risperidone and haloperidol, all of them used in low doses which did not influence per se the body temperature of m ice. All the tested antipsychotics given at high doses induced hypothe rmia in control mice; at the same time zotepine, clozapine and risperi done attenuated the hypothermic effect of mCPP. mCPP decreases the exp loratory activity of rats, this effect being considered to be mediated by 5-HT1C receptors. The tested antipsychotics, used in low doses inf luenced neither the exploratory activity nor the hypoactivity induced by mCPP. When used at higher doses they induced hypoactivity in contro l rats, the hypoactivity after joint administration of zotepine, rispe ridone or haloperidol and mCPP was significantly greater than after mC PP alone, whereas clozapine slightly attenuated the effect of mCPP. Th e obtained results indicate that zotepine did not affect the responsiv eness of 5-HT1A, and 5-HT1C receptors, but had a slight inhibitory eff ect on 5-HT1B receptors; the latter effect was shared by clozapine and risperidone, but not haloperidol. Risperidone showed a weak antagonis tic effect on 5-HT1A receptors, and clozapine - on 5-HT1C ones.