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Profound decrease of mesolimbic dopaminergic neuronal activity in morphine withdrawn rats
1Bernard B. Brodie Department of Neurosciences, University of Cagliari, Italy.
Abstract:
The spontaneous neuronal activity of meso-accumbens dopaminergic neurons was recorded in unanesthetized rats withdrawn from chronic morphine administration (15 days) by means of single cell extracellular recording techniques coupled with antidromic identification from the nucleus accumbens. Twenty-four h after last morphine administration, firing rate and burst firing were found to be drastically reduced and the relative refractory periods of the same neurons were prolonged in morphine-dependent rats as compared with chronic saline-treated controls. The number of spontaneously active dopaminergic neurons, however, did not differ between the two groups. Administration of morphine restored electrophysiological parameters. When rats were tested 2 h after last morphine administration, i.v. challenge with the opiate antagonist naloxone caused an abrupt and virtually complete reduction of dopaminergic firing rate, burst rate and a prolongation of the relative refractory period. These effects were not observed in control rats. The results indicate that the mesolimbic dopaminergic system is tonically reduced in its activity during morphine withdrawal syndrome and considering its role in the reinforcing properties of opioids, its depressed activity during the morphine withdrawal syndrome may bear relevance for the dysphoric state associated to morphine withdrawal in humans.
Insights
Morphine withdrawal drastically reduces dopamine neuron activity and firing patterns in rats. This suppressed mesolimbic dopaminergic system activity during withdrawal may explain the dysphoria associated with opioid cessation.
Area of Science:
- Neuroscience
- Pharmacology
- Neurobiology
Background:
- Chronic morphine administration leads to physical dependence.
- Opioid withdrawal is associated with significant neurobiological changes.
- The mesolimbic dopaminergic system plays a crucial role in reward and motivation.
Purpose of the Study:
- To investigate the electrophysiological properties of meso-accumbens dopaminergic neurons during morphine withdrawal.
- To determine the role of the mesolimbic dopaminergic system in the neurobiology of opioid withdrawal.
Main Methods:
- Single cell extracellular recording in unanesthetized rats.
- Antidromic identification of meso-accumbens dopaminergic neurons.
- Assessment of neuronal firing rate, burst firing, and refractory periods during morphine withdrawal and after naloxone challenge.
Main Results:
- Morphine withdrawal significantly reduced firing rate and burst firing, and prolonged relative refractory periods of dopaminergic neurons.
- Morphine administration reversed these withdrawal-induced changes.
- Naloxone challenge during withdrawal caused a near-complete cessation of dopaminergic firing.
Conclusions:
- The mesolimbic dopaminergic system exhibits tonically reduced activity during morphine withdrawal.
- This suppressed dopaminergic activity during withdrawal is relevant to the dysphoric state experienced by humans.
- The findings highlight the neurobiological underpinnings of opioid dependence and withdrawal.