Stress-opioid interactions: a comparison of morphine and methadone Ewa Taracha 1 , Pawe³ Mierzejewski 2 , Ma³gorzata Lehner 1 , Stanis³aw J. Chrapusta 3 , Maria Ka³a 4 , Wojciech Lechowicz 4 , Adam Hamed 5 , Anna Skórzewska 1 , Wojciech Kostowski 2 , Adam P³aŸnik 1,5 Department of Neurochemistry, Institute of Psychiatry and Neurology, Sobieskiego 9, PL 02-957 Warszawa, Poland Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Sobieskiego 9, PL 02-957 Warszawa, Poland Department of Experimental Pharmacology, Mossakowski Medical Research Center, Polish Academy of Sciences, Pawiñskiego 5, PL 02-106 Warszawa, Poland Institute of Forensic Research, Westerplatte 9, PL 31-033 Kraków, Poland Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Krakowskie Przedmieœcie 26/28, PL 00-927 Warszawa, Poland Correspondence: Ewa Taracha, e-mail: taracha@ipin.edu.pl 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 exam- ined 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 re- sponse 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 cingu- late 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 nonphar- macological stressors and those responding to exogenous opioids suggests that stress contributes to opioid-induced neuronal activation. Key words: opioid, stress, Fos protein, striatum, nucleus accumbens, cortex, catalepsy, pain 424