The role and therapeutic potential of 5-HT-moduline in psychiatry
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The involvement of serotonergic mechanisms in the neuropharmacology of alcohol was appreciated before it was recognized that there were multiple subtypes of serotonin (5-hydroxytryptamine; 5-HT) receptors. Thus, it was known that manipulations of the central serotonergic system could lead to a modification of the rate of tolerance development to alcohol (Frankel et al., 1975) or to a modulation of alcohol intake (Myers and Martin, 1973; Myers and Melchior, 1975) before Peroutka and Snyder (1979) first suggested that there were at least two subtypes of 5-HT receptors. Since these early reports were written, there has been a wealth of studies which have continued to support a role for 5-HT in the regulation of alcohol intake (See McBride et al., 1993b; Sellers et al., 1992, for reviews). Simultaneously, a tremendous expansion in the number of known 5-HT receptor subtypes has occurred (See Peroutka, 1988). However, there have not been, to our knowledge, any papers which have examined the possible role of specific 5-HT receptor subtypes in the regulation of alcohol's central effects. The present review addresses this deficiency in the literature. This review will focus on three major areas: the pharmacological regulation of alcohol intake; differences in 5-HT receptor subtypes among alcohol-preferring and -nonpreferring rat strains; and alterations in 5-HT receptor subtypes following chronic exposure to alcohol.
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Serotonergic agonists such as m-chlorophenylpiperazine (m-CPP) and fenfluramine may induce migraine attacks. This has led to opposing theories concerning the role of 5-hydroxytryptamine (5HT) in triggering migraine attacks; is there hyperfunction or hypofunction of the central serotonergic system. Our review of the literature strongly suggests that m-CPP and fenfluramine provoke migraine attacks by stimulating, directly or indirectly, the 5HT 2C /5HT 2B receptors, although there is no total agreement with this interpretation. Central 5HT hypersensitivity in migraine patients, probably due to 5HT neuronal depletion, is proposed on the basis of review of electrophysiological tests and neuroendocrine challenge paradigms.
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