title: GABA(A) receptors mediate the opposing roles of dopamine and the tegmental pedunculopontine nucleus in the motivational effects of ethanol.
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when an animal transitions from a non-deprived (minimal drug exposure) to a dependent (chronic drug exposure) and withdrawn state.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TPP lesions, but not a D2 receptor mutation, blocked ethanol-conditioned place preferences in ethanol-dependent and withdrawn mice.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.
authors.affiliation: Institute of Medical Science, University of Toronto, ON, Canada. r_kee@yahoo.com
authors.forename: Ryan
authors.initials: R
authors.lastname: Ting-A-Kee
authors.forename: Colleen
authors.initials: C
authors.lastname: Dockstader
authors.forename: Andrew
authors.initials: A
authors.lastname: Heinmiller
authors.forename: Taryn
authors.initials: T
authors.lastname: Grieder
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D007839:Functional Laterality; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D009042:Motivation; D009294:Narcotics / Q000494:pharmacology; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000172:deficiency; D011963:Receptors, GABA-A / Q000502:physiology*; D012054:Reinforcement, Psychology; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000523:psychology*; D013997:Time Factors
chemical_list: D018765:Dopamine Uptake Inhibitors; D018756:GABA Antagonists; D009294:Narcotics; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D000431:Ethanol; D009020:Morphine; D003042:Cocaine; D004298:Dopamine; D001640:Bicuculline