Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Jan 2005
Direct evidence for the involvement of the mesolimbic kappa-opioid system in the morphine-induced rewarding effect under an inflammatory pain-like state.
Recent clinical studies have demonstrated that when morphine is used to control pain in cancer patients, psychological dependence is not a major concern. The present study was undertaken to ascertain the modulation of psychological dependence on morphine under a chronic pain-like state in rats. The prototypical mu-opioid receptor agonist morphine (8 mg/kg, i.p.) induced a dose-dependent place preference. ⋯ These findings suggest that the inflammatory pain-like state induced by formalin injection may have caused a sustained activation of the kappa-opioidergic system within the N. Acc., resulting in suppression of the morphine-induced rewarding effect in rats. The present study provides further evidence of the clinical usefulness of morphine in patients suffering from severe pain.
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Neuropsychopharmacology · Jan 2005
Randomized Controlled Trial Clinical TrialMu-opioid self-administration vs passive administration in heroin abusers produces differential EEG activation.
Psychoactive drug self-administration (SA) produces different neurobiological effects than passive administration (PA) in non-human animals; however, such consequences have never been examined in human drug abusers. The present study compared electroencephalographic (EEG) activation produced by intravenous PA and SA of the mu-opioid fentanyl in eight heroin-dependent, methadone-stabilized male participants. In phase 1, participants received cumulative PA of fentanyl (up to 1.5 mg/70 kg; session 1), then bolus PA of placebo and fentanyl 1.5 mg/70 kg (session 2). ⋯ In phase 2, bolus fentanyl 1.5 mg/70 kg was available for SA, requiring the participant to complete 1500 responses, in each of two sessions after saline or naloxone pretreatment. Delta EEG peak amplitude increases were greater following fentanyl SA than fentanyl PA, primarily over the central midline region, and were attenuated by naloxone pretreatment. The EEG increase and its attenuation by naloxone agree with preclinical evidence and suggest that SA-related EEG responses were mediated by opioid receptors.