Mu-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). High-dose fentanyl significantly increased the amplitude of slow-frequency (delta- and theta-band) EEG activity. 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.