Serotonin and Ethanol Preference

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Abstract
This chapter brings together evidence indicating the involvement of serotonin (5-HT) in ethanol preference using data mainly obtained from selectively bred alcohol-preferring and alcohol-nonpreferring lines of rodents. Although several laboratories have established rodent lines that will consume large quantities of ethanol daily, only one line thus far has been established that satisfied all the criteria for an animal model of alcoholism and that would be suitable for studying the biological basis of ethanol preference. This is the P line of alcohol-preferring rats that: (1) freely consumes 5–9 g ethanol/kg body wt/day; (2) drinks sufficient alcohol to produce intoxicating blood alcohol concentrations; (3) works to obtain alcohol; (4) self-administers ethanol for its CNS pharmacological effects; and (5) develops chronic tolerance to and dependence on alcohol with free-choice drinking. Relative to the NP line of alcohol-nonpreferring rats, the P rat has lower 5-HT levels in several CNS regions, including some, such as the nucleus accumbens, hypothalamus, and frontal cortex, which are involved in the brain reward circuitry. Furthermore, both acute and chronic ethanol administration have effects on the 5-HT pathway from the dorsal raphe nucleus to the nucleus accumbens in the P rat. Pharmacological studies have demonstrated that fluoxetine, a serotonin uptake inhibitor, reduced the oral consumption or intragastric self-administration of alcohol in the P rats. In addition, administration of a 5-HT1B agonist also attenuated the oral intake of ethanol by P rats. It is hypothesized that the serotonergic pathway from the dorsal raphe nucleus to the nucleus accumbens is involved in the reinforcing actions of alcohol in the P line of rats.