Clonidine and yohimbine in opioid-dependent humans responding under a naloxone novel-response discrimination procedure.
Opioid-maintained volunteers were trained to distinguish between a low dose of the opioid antagonist naloxone (0.15 mg/70 kg, i.m.; i.e. Drug A) and placebo (i.e. Drug B), under an instructed novel-response drug discrimination procedure in which subjects identify the drug condition as 'A', 'B', or 'N' (neither A nor B - 'novel'). Once the discrimination was acquired, doses of naloxone, the alpha2-adrenergic antagonist yohimbine, the alpha2-adrenergic agonist clonidine, and the training dose of naloxone in combination with clonidine were tested. Naloxone and yohimbine each produced a dose-related increase and decrease in naloxone- and 'novel'-appropriate responding, respectively, with the naloxone stimulus partially generalizing to yohimbine. Clonidine produced primarily placebo-appropriate responding. Naloxone produced expected changes in self-reports, but effects of yohimbine and clonidine were unremarkable, and yohimbine was never identified as an opioid antagonist. Clonidine partially attenuated naloxone-occasioned responding in a non-dose-related manner, and attenuated some, but not all, naloxone-induced changes in self-report measures. Naloxone attenuated or enhanced several clonidine-induced changes in self-report and physiological measures. These findings indicate that adrenergic mechanisms are involved in the expression of opioid withdrawal, but the involvement is indirect.
Oliveto
A
A
Department of Psychiatry, Yale University School of Medicine, New Haven Connecticut, USA. alison.oliveto@yale.edu
Sevarino
K
K
McCance-Katz
E
E
Benios
T
T
Poling
J
J
Feingold
A
A
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D000328:Adult; D003000:Clonidine / Q000008:administration & dosage* / Q000494:pharmacology; D004192:Discrimination, Psychological; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000188:drug therapy / Q000523:psychology*; D011795:Surveys and Questionnaires; D015016:Yohimbine / Q000008:administration & dosage* / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D009292:Narcotic Antagonists; D015016:Yohimbine; D009270:Naloxone; D003000:Clonidine