RECOVERY OF CENTRAL NORADRENERGIC NEURONS ONE-YEAR AFTER THE ADMINISTRATION OF THE NEUROTOXIN DSP4

The long-term effects of the systemic administration of DSP4 (N-(2-chl oroethyl)N-ethyl-2-bromobenzylamine hydrochloride), a selective noradr energic neurotoxin, on the endogenous levels of monoamines and their m etabolites and on alpha- and beta-adrenoceptors in selected brain regi ons of the rat were examined. After 7 days, DSP4 caused a marked reduc tion (about 80%) of endogenous noradrenaline levels in locus coeruleus -innervated regions. At 90, 240 and 300 days after DSP4 injection, a p artial and gradual recovery (50%, 41% and 25% of control values, respe ctively) of the noradrenaline cortical levels was evident. One year af ter DSP4 administration, brain regional noradrenaline stores were almo st completely recovered. No changes in 5-hydroxytryptamine levels were observed in the three time intervals, but a mild decrease in cortical and hippocampal 5-hydroxyindolacetic acid levels was found 7 days aft er DSP4 injection. Following the profound noradrenaline depletion seen at 7 days, the cerebral cortical density of alpha(1)-, alpha(2)- and beta-adrenoceptors was significantly increased. Assessment of adrenerg ic receptors in cerebral cortex at 365 days after DSP4 injection, indi cated that alpha(1)- and alpha(2)-adrenoceptor densities did not diffe r from control values; however, the density of beta-adrenoceptors rema ined increased. No changes were observed in the affinities of the thre e types of adrenoceptors studied. These results indicate that after a selective noradrenergic denervation induced by DSP4, there is a slow a nd gradual recovery of noradrenaline stores and of alpha(1)- and alpha (2)-adrenoceptor populations, suggesting a possible regrowth and/or co llateral sprouting of noradrenergic terminals.