PROFOUND DECREASE OF MESOLIMBIC DOPAMINERGIC NEURONAL-ACTIVITY IN MORPHINE WITHDRAWN RATS

The spontaneous neuronal activity of meso-accumbens dopaminergic neuro ns was recorded in unanesthetized rats withdrawn from chronic morphine administration (15 days) by means of single cell extracellular record ing techniques coupled with antidromic identification from the nucleus accumbens. Twenty-four h after last morphine administration, firing r ate and burst firing were found to be drastically reduced and the rela tive 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 ele ctrophysiological parameters. When rats were tested 2 h after last mor phine administration, i.v. challenge with the opiate antagonist naloxo ne caused an abrupt and virtually complete reduction of dopaminergic f iring rate, burst rate and a prolongation of the relative refractory p eriod. These effects were not observed in control rats. The results in dicate 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 dys phoric state associated to morphine withdrawal in humans.