Ding, Zheng-MingIngraham, Cynthia M.Rodd, Zachary A.McBride, William J.2018-03-142018-03-142016-10Ding, Z.-M., Ingraham, C. M., Rodd, Z. A., & McBride, W. J. (2016). Alcohol drinking increases the dopamine-stimulating effects of ethanol and reduces D2 auto-receptor and group II metabotropic glutamate receptor function within the posterior ventral tegmental area of alcohol preferring (P) rats. Neuropharmacology, 109, 41–48. https://doi.org/10.1016/j.neuropharm.2016.05.0230028-3908https://hdl.handle.net/1805/15544Repeated local administration of ethanol (EtOH) sensitized the posterior ventral tegmental area (pVTA) to the local dopamine (DA)-stimulating effects of EtOH. Chronic alcohol drinking increased nucleus accumbens (NAC) DA transmission and pVTA glutamate transmission in alcohol-preferring (P) rats. The objectives of the present study were to determine the effects of chronic alcohol drinking by P rats on the (a) sensitivity and response of the pVTA DA neurons to the DA-stimulating actions of EtOH, and (b) negative feedback control of DA (via D2 auto-receptors) and glutamate (via group II mGlu auto-receptors) release in the pVTA. EtOH (50 or 150 mg%) or the D2/3 receptor antagonist sulpiride (100 or 200 μM) was microinjected into the pVTA while DA was sampled with microdialysis in the NAC shell (NACsh). The mGluR2/3 antagonist LY341495 (1 or 10 μM) was perfused through the pVTA via reverse microdialysis and local extracellular glutamate and DA levels were measured. EtOH produced a more robust increase of NACsh DA in the ‘EtOH’ than ‘Water’ groups (e.g., 150 mg% EtOH: to ~ 210 vs 150% of baseline). In contrast, sulpiride increased DA release in the NACsh more in the ‘Water’ than ‘EtOH’ groups (e.g., 200 μM sulpiride: to ~ 190–240 vs 150–160% of baseline). LY341495 (at 10 μM) increased extracellular glutamate and DA levels in the ‘Water’ (to ~ 150–180% and 180–230% of baseline, respectively) but not the ‘EtOH’ groups. These results indicate that alcohol drinking enhanced the DA-stimulating effects of EtOH, and attenuated the functional activities of D2 auto-receptors and group II mGluRs within the pVTA.en-USPublisher PolicyDopamineEthanolGlutamateLY341495Nucleus accumbensSulpirideVentral tegmental areaArticle