title: Stress-opioid interactions: a comparison of morphine and methadone.
abstract: The utility of methadone and morphine for analgesia and of methadone for substitution therapy for heroin addiction is a consequence of these drugs acting as opioid receptor agonists.We compared the cataleptogenic and antinociceptive effects of single subcutaneous doses of methadone hydrochloride (1-4 mg/kg) and morphine sulfate (2.5-10 mg/kg) using catalepsy and hot-plate tests, and examined the effects of the highest doses of the drugs on Fos protein expression in selected brain regions in male Sprague-Dawley rats. Methadone had greater cataleptogenic and analgesic potency than morphine. Fos immunohistochemistry revealed substantial effects on the Fos response of both the stress induced by the experimental procedures and of the drug exposure itself. There were three response patterns identified: 1) drug exposure, but not stress, significantly elevated Fos-positive cell counts in the caudate-putamen; 2) stress alone and stress combined with drug exposure similarly elevated Fos-positive cell counts in the nucleus accumbens and cingulate cortex; and 3) methadone and morphine (to a lesser extent) counteracted the stimulatory effect of nonpharmacological stressors on Fos protein expression in the somatosensory cortex barrel field, and Fos-positive cell counts in this region correlated negatively with both the duration of catalepsy and the latency time in the hot-plate test. The overlap between brain regions reacting to nonpharmacological stressors and those responding to exogenous opioids suggests that stress contributes to opioid-induced neuronal activation.
authors: Department of Neurochemistry, Institute of Psychiatry and Neurology, Sobieskiego 9, PL 02-957 Warszawa, Poland. taracha@ipin.edu.pl
authors: Ewa
authors: E
authors: Taracha
authors: Paweł
authors: P
authors: Mierzejewski
authors: Małgorzata
authors: M
authors: Lehner
authors: Stanisław J
authors: SJ
authors: Chrapusta
authors: Maria
authors: M
authors: Kała
authors: Wojciech
authors: W
authors: Lechowicz
authors: Adam
authors: A
authors: Hamed
authors: Anna
authors: A
authors: Skórzewska
authors: Wojciech
authors: W
authors: Kostowski
authors: Adam
authors: A
authors: Płaźnik
mesh_terms: D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced; D004347:Drug Interactions; D008297:Male; D008691:Methadone / Q000493:pharmacokinetics / Q000494:pharmacology*; D009020:Morphine / Q000493:pharmacokinetics / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D016760:Proto-Oncogene Proteins c-fos; D009020:Morphine; D008691:Methadone