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

卷:109

Article

Ding, Zheng-Ming¹  Ingraham, Cynthia M.¹  Rodd, Zachary A.¹  McBride, William J.¹ 

[1] Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA

关键词: Dopamine;    Ethanol;    Glutamate;    LY341495;    Nucleus accumbens;    Sulpiride;    Ventral tegmental area;   

DOI  :  10.1016/j.neuropharm.2016.05.023

来源: Elsevier

【 摘 要 】

Repeated 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 D-2 auto-receptors) and glutamate (via group II mGlu auto-receptors) release in the pVTA. EtOH (50 or 150 mg%) or the D-2/3 receptor antagonist sulpiride (100 or 200 mu M) was microinjected into the pVTA while DA was sampled with microdialysis in the NAC shell (NACsh). The mGluR(2/3) antagonist LY341495 (1 or 10 mu M) 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 similar 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 mu M sulpiride: to similar to 190-240 vs 150-160% of baseline). LY341495 (at 10 mu M) increased extracellular glutamate and DA levels in the 'Water' (to similar 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 D-2 auto-receptors and group II mGluRs within the pVTA. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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