5-HT receptors: implications for the neuropharmacology of alcohol and alcoholism

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.