Somatodendritic and postsynaptic serotonin-1A receptors in the attenuation of haloperidol-induced catalepsy.

The mechanism by which stimulation of somatodendritic and/or postsynaptic 5-hydroxytryptamine (5-HT, serotonin)-1A receptor could attenuate acute Parkinsonian-like effects of typical antipsychotics is investigated by comparing the anticataleptic and neurochemical effects of 8-hydroxy-2-di-n-propylaminotetralin (8-OH-DPAT) and buspirone in rats injected with haloperidol. Cataleptic effects of a submaximal dose (1 mg/kg) of haloperidol were attenuated more by prior administration of 8-OH-DPAT (0.25 mg/kg) than buspirone (1 mg/kg). Striatal 5-HT metabolism decreased more in buspirone- than 8-OH-DPAT-injected animals. Administration of haloperidol did not alter 5-HT metabolism in saline-, 8-OH-DPAT- or buspirone-injected animals. Dopamine decreased and its metabolite homovanillic acid (HVA) increased in the striatum of rats injected with buspirone. Effects of 8-OH-DPAT on dopamine metabolism were not significant. Haloperidol-induced increases of dopamine metabolites were attenuated by prior administration of 8-OH-DPAT, but not buspirone. The mechanism by which stimulation of somatodendritic as well as postsynaptic 5-HT-1A receptors could attenuate haloperidol-induced catalepsy is discussed. The findings have potential implications in the treatment of schizophrenia and motor behavior.