The opioid mechanism of interferon-alpha action.
Rats were trained to discriminate the opioid receptor agonist ethylketocyclazocine (EKC) (0.3 mg/kg body weight, intraperitoneally) from saline. Interferon-alpha (IFN-alpha), when substituted for EKC, elicited a dose-related increase in EKC-like responses. This generalization of EKC responses was blocked by the opioid antagonist naloxone (1 mg/kg). Potentiation of responses to a low dose (0.1 mg/kg) of EKC by IFN-alpha (1 x 10(6) U/kg or 0.22 nmol/kg) was also observed. Data thus indicate the involvement of opioid neurons on the action of IFN-alpha. d-Amphetamine (0.8 mg/kg) was shown to potentiate both EKC (0.1 mg/kg) and IFN-alpha (1 x 10(6) U/kg). The present study confirms our previously proposed opioid-mediated dopaminergic mechanism of IFN-alpha.
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Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
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Fan
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Meyers
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Tansey
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Payne
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Levin
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D000818:Animals; D003913:Dextroamphetamine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016314:Ethylketocyclazocine / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects; D005793:Generalization, Psychological; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects*
D016898:Interferon-alpha; D011957:Receptors, Opioid; D009270:Naloxone; D016314:Ethylketocyclazocine; D003913:Dextroamphetamine