5-Hydroxytryptamine and alcoholism

Abstract

Ethanol interferes with several brain functions, namely with specific neurotransmission processes. Depletion of brain 5-hydroxytryptamine (5-HT) impairs the acquisition of tolerance to ethanol or facilitates its loss, while activation of 5-HT brain transmission facilitates tolerance development and decreases ethanol consumption. One hypothesis which has been put towards is that genetically determined low 5-HT brain levels may be related to a predisposition to alcoholism. Acute ethanol intake transiently increases brain 5-HT turnover; therefore, ethanol consumption might be hypothesized as an attempt to correct a deficit of 5-HT brain transmission. The findings that administration of selective 5-HT neuronal uptake blockers (zimelidine, citalopram, fluvoxamine and fluoxetine) decrease ethanol intake has given further support to this hypothesis. However, the time course of this effect is different from the antidepressant action described for these compounds. Also, there is evidence to suggest that lower doses of the 5-HT uptake blockers are needed in order to reduce ethanol intake in alcoholic patients; this, however, requires further investigation. Interestingly, other clinical entities which have been found to be associated with a hypothetical dysfunction in 5-HT brain transmission, such as obsessive compulsive disorder, panic disorder and some forms of depression, have also been associated with alcoholism, and seem to respond as well to 5-HT neuronal uptake blockers.

Modulation of agonist and antagonist interactions in serotonin 1A receptors by alcohols

“…Both animal and human studies suggest the involvement of the serotonergic system in ethanol preference and dependence [10, 22]. However, there have been very few studies, at the molecular level, on the effects of alcohols on ligand binding properties of the isolated receptors.…”

“…Serotonergic signalling has been shown to play an important role in the regulation of alcohol intake, preference and dependence [10, 21–24]. Several groups have found alterations in serotonin receptor subtypes in different regions of the rodent brain associated with alcohol tolerance and dependence [24].…”