Serotonin Receptors and Antipsychotic Drug Action
The effect of serotonin (5-HT) to modulate dopaminergic activity in the nigrostriatal system has been known for some time (Dray et al. 1976). Generally, 5-HT has an inhibitory effect on dopaminergic output (see Meltzer and Nash 1991, for review). However, there is also evidence that 5-HT can enhance some aspects of dopaminergic function; thus, an over-simplistic one-way model should not be considered (Meltzer and Nash 1991). The effect of 5-HT in modulating dopaminergic activity is mediated via specific 5-HT receptors, the nature of which will be discussed subsequently. Due to the central role that antagonism of dopamine (DA) receptors has in the ability of antipsychotic drugs to reduce psychotic symptoms and in producing side effects such as extrapyramidal symptoms, tardive dyskinesia, and stimulation of prolactin secretion (Meltzer and Stahl 1976), it is necessary to consider whether serotonergic influences modulate the action of at least some antipsychotic drugs. As will be discussed, it has been suggested that serotonergic effects are particularly relevant to the action of clozapine and some other so-called atypical antipsychotic drugs (see Meltzer 1989; Deutch et al. 1991, for reviews). This article will consider the evidence for the action of antipsychotic drugs on specific 5-HT receptors as a contributing factor to their antipsychotic action or unique side effect profile.
KeywordsNucleus Accumbens Antipsychotic Drug Prolactin Secretion Dopaminergic Activity Atypical Antipsychotic Drug
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