5-HT2A and 5-HT2C/5-HT1B Receptors Are Differentially Involved in Alcohol Preference and Consummatory Behavior in cAA Rats

Abstract

The present study aimed to investigate the role of serotonin 5-HT2A and 5-HT2C receptors in the control of alcohol preference and consummatory behavior in alcohol-preferring cAA rats. Effects of the 5-HT2A/2C receptor agonist, DOI, the 5-HT2C/1B receptor agonist, mCPP, the 5-HT2A/2C receptor antagonist, ritanserin, and the 5-HT2A receptor antagonist, MDL 100,907, on ethanol (EtOH, 10% v/v) preference and intake, as well as total fluid and food intake were evaluated in a 12-h limited-access two-bottle paradigm. DOI (0.3–3 mg/kg, IP) reduced EtOH intake and preference, but not total fluid or food intake; whereas mCPP (1–10 mg/kg, SC) reduced EtOH, total fluid, and food intake. Therefore, it is concluded that DOI induces a specific and selective antialcohol effect, whereas mCPP rather induces a general suppressive effect on consummatory behavior. Ritanserin (1–10 mg/kg, IP) did not affect EtOH intake and preference, nor total fluid and food consumption. MDL 100,907 (0.1–1 mg/kg, IP) induced only a small reduction of food intake at the highest dose tested. Pretreatment with ritanserin (3 mg/kg, IP) and MDL 100,907 (0.3 mg/kg, IP) blocked the effects of DOI (3 mg/kg, IP), but not those of mCPP (10 mg/kg, IP). It is suggested that activation of 5-HT2C and/or 5-HT1B receptors results in a general decrease of consummatory behavior, whereas activation of 5-HT2A receptors selectively decreases EtOH intake and preference, as assessed in the cAA rat model of alcoholism.