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.
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 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.
Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: zding@iupui.edu.
Zheng-Ming
ZM
Ding
Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Cynthia M
CM
Ingraham
Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Zachary A
ZA
Rodd
Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
William J
WJ
McBride
D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists / Q000008:administration & dosage; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D017551:Microdialysis; D008845:Microinjections; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D000431:Ethanol; D004298:Dopamine
Dopamine; Ethanol; Glutamate; LY341495; Nucleus accumbens; Sulpiride; Ventral tegmental area