Opioid receptors and neuropeptides in the CNS in rats treated chronically with amoxapine or amitriptyline.
The central mechanism responsible for the potentiation by antidepressant drugs of analgesia induced by morphine, was explored by measuring the levels of various neuropeptides (met-enkephalin, leu-enkephalin, dynorphin, substance P and cholecystokinin-like materials) and the density of delta and mu opioid binding sites in the spinal cord of rats treated for 14 days with amoxapine (10 mg/kg i.p., daily) or amitriptyline (10 mg/kg i.p., daily). Similar measurements were made in the hypothalamus and cerebral cortex for comparison. Chronic treatment with amoxapine or amitriptyline did not affect the levels of dynorphin, substance P and cholecystokinin, but markedly enhanced the levels of leu-enkephalin in the three structures examined. The levels of met-enkephalin were also increased after treatment with amitriptyline but only in the spinal cord and hypothalamus. No changes in opioid receptors were found in the cerebral cortex, but the densities of delta and mu opioid binding sites were increased in the spinal cord, and decreased in the hypothalamus of rats treated with amoxapine or amitriptyline. These changes induced by antidepressants in opioidergic markers at the spinal level might account for the potentiation of the action of morphine in amoxapine- or amitriptyline-treated rats. In addition, the observed alterations in the same markers in the hypothalamus could be associated with changes induced by antidepressants in neuroendocrine regulation.
D000639:Amitriptyline / Q000494:pharmacology; D000657:Amoxapine / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects; D004357:Drug Synergism; D007031:Hypothalamus / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects
D000929:Antidepressive Agents, Tricyclic; D009479:Neuropeptides; D011957:Receptors, Opioid; D011985:Receptors, Serotonin; D000639:Amitriptyline; D009020:Morphine; D000657:Amoxapine