Neurochemical activity of noradrenergic neurons and pituitary-adrenal response after naloxone-induced withdrawal: the role of calcium channels.
The influence of the L-type calcium channel antagonist nimodipine on both the activity of noradrenergic neurons projecting to the hypothalamus and the pituitary-adrenal response during morphine tolerance and withdrawal was analysed. Tissue concentration of hypothalamic noradrenaline (NA) and its metabolite 3-methoxy-4-hydroxy-phenylethylen-glycol (MHPG) were determined by high-pressure liquid chromatography. Plasma corticosterone concentration (a marker of pituitary-adrenal activity) was measured by radioimmunoassay. Rats rendered tolerant to morphine decreased hypothalamic MHPG concentration, and reduced hypothalamic NA turnover. Chronic infusion of nimodipine concurrently with morphine prevented the decrease in NA turnover during tolerance. After naloxone administration to tolerant rats we found a striking parallelism between an increased activity of the hypothalamic-pituitary-adrenal axis and an enhanced activity of noradrenergic neurons projecting to the hypothalamus. However, hypothalamic NA turnover and MHPG concentration, both elevated during withdrawal, returned to control levels in rats infused chronically with nimodipine, concomitantly with a reduction of the secretion of corticosterone. Taken together, these data indicate that increased noradrenergic neuronal activity in the hypothalamic nerve terminals is associated with the neuroendocrine morphine withdrawal syndrome and suggest that an up-regulated calcium system might contribute to the activation of these neurons.
Vargas
M L
ML
Unit of Pharmacology, University School of Medicine, Murcia, Spain.
Martínez-Piñero
M G
MG
Milanés
M V
MV
D000311:Adrenal Glands / Q000187:drug effects*; D000320:Adrenergic Fibers / Q000187:drug effects*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D015220:Calcium Channels; D009270:Naloxone