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GABA A receptors mediate the opposing roles of dopamine and the tegmental pedunculopontine nucleus in the motivational effects of ethanol
Author(s) -
TingAKee Ryan,
Dockstader Colleen,
Heinmiller Andrew,
Grieder Taryn,
Van Der Kooy Derek
Publication year - 2009
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2009.06684.x
Subject(s) - ventral tegmental area , pedunculopontine tegmental nucleus , dopamine , chemistry , neuroscience , conditioned place preference , pedunculopontine nucleus , dopamine receptor , pharmacology , psychology , medicine , dopaminergic , nucleus , biology , parkinson's disease , deep brain stimulation , disease
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when an animal transitions from a non‐deprived (minimal drug exposure) to a dependent (chronic drug exposure) and withdrawn state.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TPP lesions, but not a D2 receptor mutation, blocked ethanol‐conditioned place preferences in ethanol‐dependent and withdrawn mice.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.