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Behavioral/Systems/Cognitive No Effect of Morphine on Ventral Tegmental Dopamine
 

Summary: Behavioral/Systems/Cognitive
No Effect of Morphine on Ventral Tegmental Dopamine
Neurons during Withdrawal
Franc¸ois Georges,1 Catherine Le Moine,1 and Gary Aston-Jones2
1Centre National de la Recherche Scientifique, Unite´ Mixte de Recherche 5541 "Interactions Neuronales et Comportements," Universite´ Victor Segalen,
33076 Bordeaux Cedex, France, and 2 Laboratory for Neuromodulation and Behavior, Department of Psychiatry, University of Pennsylvania School of
Medicine, Translational Research Laboratories, Philadelphia, Pennsylvania 19104-3403
Substantial evidence indicates that the ventral tegmental area (VTA) of the mesocorticolimbic dopaminergic (DA) system has a key role
in mechanisms of opiate dependence. Although DA neurons have been studied extensively, little is known about their activity and their
response to acute morphine during morphine dependence. We recorded the activity of VTA DA neurons in five groups of anesthetized
rats: drug-naive (naive) rats, morphine-dependent [(MD) implanted with pellets] rats, and three groups of withdrawn rats. Withdrawals
either were precipitated by naltrexone or occurred spontaneously 24 h or 15 d after pellet removal. We confirmed that acute morphine in
naive rats produced a marked increase in the firing of VTA DA neurons. We also found that the basal firing rate of VTA DA neurons was
markedlyhigherinMDthaninnaiverats;however,inMDrats,acutemorphinefailedtoincreaseDAactivity.Weconfirmedinhibitionof
VTA DA activity in MD rats in response to precipitated withdrawal; however, this inhibition resulted only in a normalization of the firing
ratetothatofnaiveanimals.Inratsthathadspontaneouswithdrawalafter24hor15d,theactivityofVTADAneuronswassimilartothat
of naive rats, and an acute injection of morphine failed to alter their activity. Our results indicate that VTA DA neurons show long-lasting
tolerancetotheacuteeffectofmorphineafterwithdrawal.ThesefindingsshowthatVTADAneuralactivityisunlikelytobeafactorinthe
altered behavioral responses that occur with acute morphine or naltrexone administration after chronic opiate exposure.
Key words: addiction; withdrawal; opiates; ventral tegmental area; naltrexone; extracellular recording

  

Source: Aston-Jones, Gary - Department of Neurosciences, Medical University of South Carolina

 

Collections: Biology and Medicine