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  • Title: GABA(A) receptors mediate the opposing roles of dopamine and the tegmental pedunculopontine nucleus in the motivational effects of ethanol.
    Author: Ting-A-Kee R, Dockstader C, Heinmiller A, Grieder T, van der Kooy D.
    Journal: Eur J Neurosci; 2009 Mar; 29(6):1235-44. PubMed ID: 19302158.
    Abstract:
    Recent work has demonstrated that changes in ventral tegmental area (VTA) GABA(A) receptor ion conductance properties are responsible for switching morphine's positive reinforcing properties from a dopamine-independent to a dopamine-dependent pathway when an animal transitions from a non-deprived (minimal drug exposure) to a dependent (chronic drug exposure) and withdrawn state. Here we show that a double dissociation of ethanol's positive reinforcing properties is exactly opposite to that seen with morphine. In C57BL/6 mice, ethanol-conditioned place preferences were blocked in dopamine D2 receptor knockout non-deprived mice, but not by a lesion of the tegmental pedunculopontine nucleus (TPP). On the other hand, TPP lesions, but not a D2 receptor mutation, blocked ethanol-conditioned place preferences in ethanol-dependent and withdrawn mice. The opposite effects of ethanol and opiates can be explained by their proposed actions through a common VTA GABA(A) receptor switching mechanism.
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