Reduced 5-HT₃ receptor binding and lower baseline plus maze anxiety in the alcohol-preferring inbred fawn-hooded rat

The present investigation sought to explore the relationship between the 5-HT₃ receptor and anxiety-like behavior in fawn-hooded (FH/Wjd) rats, an inbred strain that exhibits a high intake and preference for ethanol, and the alcohol-nonpreferring ACI/N strain. Using quantitative autoradiography, we examined whether there were differences in central 5-HT₃ receptor binding in FH/Wjd versus ACI/N rats. Ten to 14 days prior to being used in the autoradiographic studies, rats were first confirmed to be representative of their strains by subjecting them to a two-bottle choice procedure for 2 weeks. The binding of [³H]LY 278584 to 5-HT₃ receptors was significantly reduced in frontal cortex, CA1 region of hippocampus, and in the medial and lateral nuclei of the amygdala of FH/Wjd versus ACI/N rats. In the anterior cingulate cortex and in the dentate gyrus region of the hippocampus the reduction in [³H]LY 278548 binding in the FH/Wjd versus ACI/N strain (40% and 41%, respectively) did not reach statistical significance. In a separate group of animals, the effects of the 5-HT₃ receptor antagonist MDL 72222 (3 mg/kg ip) on anxiety-related behaviors were assessed in the elevated plus maze. In vehicle-treated rats, the FH/Wjd strain exhibited significantly greater percent of time spent on the open arms and percent open arm entries, an indication of less anxiety. Pretreatment with MDL 72222 did not alter these behaviors in the FH/Wjd rats, but had an anxiolytic-like effect in the ACI/N strain, significantly increasing the percent of time spent on the open arms and percent open arm entries. Further research into 5-HT₃ receptor function in the alcohol-preferring FH/Wjd rats is needed to elucidate the relationship among 5-HT₃ receptors, alcohol drinking, and anxiety.