Original Investigation

Psychopharmacology

, Volume 139, Issue 1, pp 79-85

Ethanol and negative feedback regulation of mesolimbic dopamine release in rats

  • R. R. KohlAffiliated withDepartment of Psychiatry, Institute of Psychiatric Research, and Graduate Program in Medical Neurobiology, Indiana University School of Medicine, Indianapolis, IN 46202-4887, USA
  • , J. S. KatnerAffiliated withDepartment of Psychiatry, Institute of Psychiatric Research, and Graduate Program in Medical Neurobiology, Indiana University School of Medicine, Indianapolis, IN 46202-4887, USA
  • , E. ChernetAffiliated withDepartment of Psychiatry, Institute of Psychiatric Research, and Graduate Program in Medical Neurobiology, Indiana University School of Medicine, Indianapolis, IN 46202-4887, USA
  • , W. J. McBrideAffiliated withDepartment of Psychiatry, Institute of Psychiatric Research, and Graduate Program in Medical Neurobiology, Indiana University School of Medicine, Indianapolis, IN 46202-4887, USA

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Abstract

 The objectives of this study were to examine the relationship between somatodendritic and terminal field dopamine (DA) release following manipulation of DA D2 receptors in the ventral tegmental area (VTA), systemic administration of ethanol, and inhibition of DA uptake in the nucleus accumbens (ACB). Perfusion of 5, 25 and 100 μM quinpirole (a D2 agonist), or sulpiride (a D2 antagonist) through the microdialysis probe in the VTA produced dose-related decreases or increases, respectively, in the extracellular levels of DA in both the VTA and ACB of adult Wistar rats. The IP administration of 2–3 g/kg ethanol produced a sustained increase in the extracellular levels of DA (150–200% of baseline) in the ACB for at least 2 h after injection, whereas only a transient increase was observed in the VTA. Local perfusion of the ACB with 100 μM GBR12909, a DA uptake inhibitor, elevated the extracellular levels of DA in the ACB to approximately 400% of baseline, but decreased the extracellular levels of DA in the VTA to approximately 50% of baseline. Overall, the results suggest that (a) there is an association between somatodendritic and terminal field DA release when D2 cell body autoreceptors in the VTA are manipulated, (b) elevating synaptic levels of DA in the terminal field activates a long-loop negative feedback system to the VTA, and (c) different mechanisms may be mediating the actions of ethanol on DA neuronal activity and terminal DA release.

Key words Ventral tegmental area Nucleus accumbens Somatodendritic dopamine release Dopamine release Quinpirole Sulpiride GBR12909 Dopamine D2 autoreceptors