“…Here we confirmed that acute morphine in naive rats produced a marked increase in the firing of VTA DA neurons (Gysling and Wang, 1983;Matthews and German, 1984). Morphine dependence also increased the firing rate of VTA DA neurons compared with naive animals and produced a shift to the right in the firing rate distribution; however, our results also showed that, in dependent or withdrawal rats, an acute injection of morphine failed to increase the activity of DA neurons.…”
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anesthetized rats: drug-naive (naive) rats, morphine-dependent [(MD) implanted with pellets] rats, and three groups of withdrawn rats.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.
“…Here we confirmed that acute morphine in naive rats produced a marked increase in the firing of VTA DA neurons (Gysling and Wang, 1983;Matthews and German, 1984). Morphine dependence also increased the firing rate of VTA DA neurons compared with naive animals and produced a shift to the right in the firing rate distribution; however, our results also showed that, in dependent or withdrawal rats, an acute injection of morphine failed to increase the activity of DA neurons.…”
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.
“…133 This coincides with increased firing of dopaminergic neurons in the VTA with acute IV morphine. 134 Naloxone reversed this effect. The putative mechanism by which morphine increases dopaminergic firing is via coupling of MOP to Gα i and Gα o proteins and causing hyperpolarization of local GABAergic interneurons in the VTA.…”
Section: Molecular Changes In the Ventral Tegmental Areamentioning
“…Opiate receptors of the m-type are not directly situated on the dopaminergic mesocorticolimbic neurons, but on GABAergic interneurons and GABAergic afferents to the VTA. Stimulation of these receptors leads to inhibition of both tonic and phasic release of GABA, which is secondary followed by disinhibition of dopaminergic VTA neurons (Gysling and Wang, 1983;Dilts and Kalivas, 1989;Pontieri et al, 1996). On the other hand, m opiate receptors are also found on GABAergic neurons of the NA, which receive the dopaminergic projections from the VTA neurons (Dilts and Kalivas, 1989).…”
The acute influence of ethanol on cerebral activity induces complex psycho-physiological effects that are considerably more pronounced during acute ethanol influx than during maximal blood alcohol concentration (elimination phase). Despite the psychiatric and forensic relevance of these different ethanol effects, the underlying neuronal mechanisms are still unclear. In total, 20 male healthy volunteers were investigated each with three different experimental conditions in a randomized order using an intravenous ethanol challenge (40 g bolus infusion): during influx phase, elimination phase, and under placebo condition. During and after the ethanol (or placebo) infusion, neuropsychological testing of divided attention for visual and auditory stimuli was performed with subsequent 18-FDG PET acquisition. The PET data were analysed using SPM99. Ethanol influx and elimination phase showed focal activations in the bilateral striatum and frontal cortex and deactivations in the occipital cortex. The comparison of influx phase vs elimination phase revealed activations in the anterior cingulate and right prefrontal cortex, relevant deactivations were found in the left superior temporal cortex including Wernicke's area. Neuropsychological testing showed an attentional impairment under ethanol influx compared to ethanol elimination and placebo with an inverse correlation of the attentional performance for auditory stimuli to occipital activity and for visual stimuli to the left temporal (including auditory) cortex. Acute ethanol administration in healthy volunteers stimulates those striatal regions that are considered to have a particular relevance for alcohol craving ('reward system'). Modality specific reciprocal inhibition of sensory cortex activity seems to be relevant for attentional performance during acute alcohol impact.
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