By using various 5-HT receptor subtype selective antagonists, we have demonstrated that m-chlorophenylpiperazine (m-CPP, a 5-HT1 agonist )-induced prolactin secretion is mediated by stimulation of postsynaptic 5-HT1C receptors while corticosterone secretion may be mediated by an antagonistic effect at 5-HT3 receptors or by non-serotonergic mechanisms. The food intake suppressant effect of the hallucinogenic agent, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) was demonstrated to be mediated by stimulation of both 5-HT1C and 5-HT2 receptors. In another study, we have demonstrated that clonidine stimulates growth hormone secretion by activation of alpha2-heteroreceptors present on 5-HT nerve terminals which, in turn, enhance 5-HT activity by stimulation of post synaptic 5-HT1C receptors to promote growth hormone releasing factor. Furthermore, either 5-HT1C receptors or alpha2-adrenergic heteroreceptors or both are functionally subsensitive in the Fawn-Hooded rat strain relative to the Wistar rat strain. In a separate series of experiments, chronic treatment with the tricyclic antidepressants and clorgyline (MAO type A inhibiting antidepressant) decreased the steady state concentrations of G protein alpha subunit Gs-alpha and; to a lesser extent Gi-alpha in several brain regions, while Go-alpha was increased by tricyclics but not clorgyline. Chronic treatment with carbamazepine decreased Gs-alpha in several brain areas reaching significance in the neostriatum, while chronic lithium treatment had no unequivocal effect. Lithium treatment significantly increased Gi-alpha in the hypothalamus and hippocampus, whereas carbamazepine decreased Gi-alpha in the frontal cortex. These findings indicate that long-term treatment with antidepressant and antibipolar drugs exert differential effects on G protein alpha subunits, and that antidepressant or antibipolar efficacy may potentially be based on functional modifications of signal transduction.
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