Opiate state controls bi-directional reward signaling via GABAA receptors in the ventral tegmental area.
The neural mechanisms that mediate the transition from a drug-naive state to a state of drug dependence and addiction are not yet known. Here we show that a discrete population of GABA(A) receptors in the mammalian ventral tegmental area (VTA) serves as a potential addiction switching mechanism by gating reward transmission through one of two neural motivational systems: either a dopamine-independent (opiate-naive) or a dopaminergic (opiate-dependent or opiate-withdrawn) system. Bi-directional transmission of reward signals through this GABA(A) receptor substrate is dynamically controlled by the opiate state of the organism and involves a molecular alteration of the GABA(A) receptor. After opiate exposure and subsequent withdrawal, the functional conductance properties of the rat VTA GABA(A) receptor switch from an inhibitory to an excitatory signaling mode.
Laviolette
Steven R
SR
Neurobiology Research Group, Department of Anatomy and Cell Biology, University of Toronto, Ontario M5S 1A8, Canada. laviolette@bns.pitt.edu
Gallegos
Roger A
RA
Henriksen
Steven J
SJ
van der Kooy
Derek
D
D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage; D002256:Carbonic Anhydrases / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018755:GABA Agonists / Q000008:administration & dosage; D018756:GABA Antagonists / Q000008:administration & dosage; D003932:Heroin / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009118:Muscimol / Q000008:administration & dosage; D009294:Narcotics / Q000494:pharmacology; D009293:Opioid-Related Disorders; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D018755:GABA Agonists; D018756:GABA Antagonists; D009294:Narcotics; D011963:Receptors, GABA-A; D009118:Muscimol; D003932:Heroin; D002256:Carbonic Anhydrases; D004298:Dopamine; D001640:Bicuculline