5-HT transporter sites and 5-HT1A and 5-HT3 receptors in fawn-hooded rats:: A quantitative autoradiography study

Background: The neuroanatomical profiles of 5-HT1A receptors, 5-HT3 receptors, and 5-HT transporters (5-HTT) in the brain of the Fawn-Hooded (FH) rat, particularly mesocorticolimbic regions, are not fully elucidated. Methods: By means of in vitro quantitative autoradiography, we used [H-3]citalopram, [H-3]8-OH-DPAT, and [H-3]GR65630 to label 5-HTT, 5-HT1A receptors, and 5-HT3 receptors in the brain of alcohol-naive FH rats, Wistar-Kyoto (WKY) rats, and FH rats given free access to 5% ethanol and/or after 24 to 48 hr withdrawal. Results and Conclusions: In alcohol-naive rats, FH rats displayed significantly higher (p < 0.05) densities of [H-3]citalopram binding in the nucleus accumbens (+30%), lateral septum (+37%), ventral pallidum (+21%), and ventral tegmental area (+24%), as well as an increased binding of [H-3]8-OH-DPAT to 5HT(1A) receptors in the frontal and parietal cortex (+33%), occipital and temporal cortex (+25%), and hippocampal CA3 region (+31%), compared with WKY rats, whereas both strains exhibited comparable [H-3]GR65630 binding to 5-HT3 receptors. Compared with control FH (naive) rats, chronic ethanol consumption significantly decreased (p < 0.05) [H-3]8-OH-DPAT binding in the frontal and parietal cortex (-15%) but significantly increased binding (p < 0.05) in the entorhinal cortex (+25%), retrosplenial granular cortex (+20%), and hippocampal CA1 (+14%) and CA3 regions (+18%). Moreover, ethanol withdrawal induced the same extent of increased [3H]8-OH-DPAT binding in the entorhinal and retrosplenial cortex as seen in FH (chronic) rats. In contrast, [H-3]8-OH-DPAT binding in the hippocampal CA1 and CA3 regions was decreased by -9% and -20% from the level of chronic ethanol-treated FH rat (p < 0.05) and returned to the control level seen in FH (naive) rats. Significance: The elevated 5-HT transporters and 5-HT1A receptors in the mesocorticolimbic areas in FH rats may reflect a potential innate altered transmission at serotonergic synapses, which possibly may affect the high intake of alcohol in FH rats. The region-specific alterations of 5-HT1A receptors in FH rat brain after ethanol challenges suggest that 5-Ht(1A) receptors are sensitive to ethanol challenges, whereas 5-HTT are apparently insensitive.