Clonidine fails to modify dopaminergic neuronal activity during morphine withdrawal

Rationale: Cellular substrates of opiate withdrawal syndrome involve severa l brain areas, in particular the mesolimbic dopaminergic and noradrenergic systems, but the interactions between the two pathways remain unclear. Obje ctives: The aim of the present work was to investigate the effects of the a lpha (2)-agonist clonidine on ventral tegmental area dopamine neurons durin g morphine withdrawal syndrome by recording their neuronal activity before and after the administration of low and relatively high doses of clonidine (from 5 to 100 mug/kg). Methods: The spontaneous neuronal activity of mesoa ccumbens dopaminergic neurons, identified by anti-dromical stimulation from the nucleus accumbens, was recorded by use of in vivo extracellular single -unit recordings in control and morphine-withdrawn rats after chronic admin istration (15 days). Results: Control rats showed a mean spontaneous firing frequency of 2.47 +/- 0.48 Hz, percentage of burst firing of 22 +/- 12 and an increase in firing after the administration of cumulative doses of clon idine (5, 10, 20, 40, 100 mug/kg). Conversely, both spontaneous firing rate (1.55 +/- 0.25 Hz) and the percentage of burst firing (5 +/- 2) were found to be significantly reduced in rats abstinent for 24 h, and increasing dos es of clonidine did not re-establish electrophysiological activity observed in the controls. Conclusion: The results indicate that: 1) clonidine did n ot restore the decreased firing activity of DA neurons in morphine-withdraw n rats, and 2) high doses of clonidine increased firing in control rats but not in morphine-withdrawn rats.