The reinforcing effects of ethanol within the posterior ventral tegmental area depend upon dopamine neurotransmission to forebrain cortico-limbic systems

摘要

Ethanol can be self-infused directly into the posterior ventral tegmental area (pVTA) and these effects involve activation of local dopamine neurons. However, the neuro-circuitry beyond the pVTA involved in these reinforcing effects has not been explored. Intra-pVTA micro-injection of ethanol increases dopamine release in the nucleus accumbens (NAC), medial prefrontal cortex (mPFC) and ventral pallidum (VP). The current study tested the hypothesis that the reinforcing effects of ethanol within the pVTA involve activation of dopamine projections from the pVTA to the NAC, VP, and mPFC. Following the acquisition of self-infusions of 200 mg% ethanol into the pVTA, either the dopamine D2 receptor antagonist sulpiride (0, 10 or 100 µM), or the D1 receptor antagonist SCH-23390 (0, 10 or 100 µM) was micro-injected into the ipsilateral NAC shell (NACsh), NAC core (NACcr), VP or mPFC immediately prior to the self-infusion sessions to assess the involvement of the different dopamine projections in the reinforcing effects of ethanol. Microinjection of each compound at the higher concentration into the NACsh, VP or mPFC, but not the NACcr, significantly reduced the responses on the active lever (from 40–50 to approximately 20 responses). These results indicate that activation of dopamine receptors in the NACsh, VP, or mPFC, but not the NACcr, is involved in mediating the reinforcing effects of ethanol in the pVTA, suggesting that the ‘alcohol reward’ neuro-circuitry consist of, at least in part, activation of the dopamine projections from the pVTA to the NACsh, VP and mPFC.