M. Diana et al., PROFOUND DECREASE OF MESOLIMBIC DOPAMINERGIC NEURONAL-ACTIVITY IN MORPHINE WITHDRAWN RATS, The Journal of pharmacology and experimental therapeutics, 272(2), 1995, pp. 781-785
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ns was recorded in unanesthetized rats withdrawn from chronic morphine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.