Evaluation of the supraspinal analgesic activity and abuse liability of ethylketocyclazocine

Rats were trained to escape from aversive electrical brain stimulation delivered to the midbrain reticular formation (MRF) or to obtain rewarding intracranial stimulation delivered to the medial forebrain bundle (MFB). The threshold for escape behavior was determined by a modification of the psychophysical method of limits. Likewise, reward thresholds were determined by a rate-free psychophysical method. Acute administration of ethylketocyclazocine (EKC) (0.06-1.0 mg/kg s.c.) raised escape threshold in a dose-dependent manner while having no effect on non-specific measures of sedation or motor impairment. This suggests that opioids with kappa receptor activity specifically modulate pain at a supraspinal level. Administration of EKC had no effect on the threshold for rewarding intracranial stimulation to the MFB suggesting that EKC has low potential for abuse.