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Profound decrease of mesolimbic dopaminergic neuronal activity in morphine withdrawn rats

M Diana¹, M Pistis, A Muntoni

¹Bernard B. Brodie Department of Neurosciences, University of Cagliari, Italy.

The Journal of Pharmacology and Experimental Therapeutics

|February 1, 1995

Summary

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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.

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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.