No effect of morphine on ventral tegmental dopamine neurons during withdrawal
Journal of Neuroscience. 2006-05-24; 26(21): 5720-5726
Lire sur PubMed
1. J Neurosci. 2006 May 24;26(21):5720-6.
No effect of morphine on ventral tegmental dopamine neurons during withdrawal.
Georges F(1), Le Moine C, Aston-Jones G.
(1)Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5541
Interactions Neuronales et Comportements, Université Victor Segalen, 33076
Bordeaux Cedex, France.
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with pellets] rats, and three groups of withdrawn rats.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 markedly higher in MD than in naive rats; however, in
MD rats, acute morphine failed to increase DA activity. We confirmed inhibition
of VTA DA activity in MD rats in response to precipitated withdrawal; however,
this inhibition resulted only in a normalization of the firing rate to that of
naive animals. In rats that had spontaneous withdrawal after 24 h or 15 d, the
activity of VTA DA neurons was similar to that of naive rats, and an acute
injection of morphine failed to alter their activity. Our results indicate that
VTA DA neurons show long-lasting tolerance to the acute effect of morphine after
withdrawal. These findings show that VTA DA neural activity is unlikely to be a
factor in the altered behavioral responses that occur with acute morphine or
naltrexone administration after chronic opiate exposure.
PMID: 16723528 [Indexed for MEDLINE]