Serotonergic modulation of dopamine neurotransmission: a mechanism for enhancing therapeutics in schizophrenia.

Although the principal mechanism by which all antipsychotic drugs act is the blockade of dopamine D-2 receptors, typical antipsychotics given in doses within the clinically effective range induce extrapyramidal symptoms (EPS). Serotonin Hydroxytryptamine, 5-HT can modulate the activity of dopaminergic neurons, while the activity of atypical antipsychotic agent towards serotonin receptors is involved in the ability of these agents to produce fewer EPS. In order to extend therapeutics in schizophrenia, it is important to examine the serotonergic modulation of neuroleptic activity. This review analyzes differences in neurochemical, behavioral and pharmacological profiles of typical and atypical antipsychotics and the role of serotonin receptors in the attenuation of EPS-induced by the typical neuroleptics. In addition to blocking dopamine receptors, the atypical antipsychotics also have affinities for serotonin receptors. Serotonergic modulation of motor activity appears primarily of inhibitory type. Stimulation of somatodendritic 5-HT-1A receptors decreases the availability of 5-HT at inhibitory 5-HT-2C receptors located on dopaminergic neurons to attenuate acute parkinsonian-like effects of typical antipsychotics. An increase in the effectiveness of pre and postsynaptic 5-HT-1A receptors following long-term administration of haloperidol raises the possibility that 5-HT agonists may also prove useful for the alleviation of late appearing tardive dyskinesias. Clinicians can now apply the knowledge of serotonergic modulation of neuroleptic action to the treatment of schizophrenic patients by using selected serotonergic anxiolytics and antidepressants as adjuvants in the treatment of schizophrenia.