Profound decrease of mesolimbic dopaminergic neuronal activity in morphine withdrawn rats.

The spontaneous neuronal activity of meso-accumbens dopaminergic neurons was recorded in unanesthetized rats withdrawn from chronic morphine administration (15 days) by means of single cell extracellular recording techniques coupled with antidromic identification from the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.