Mu-opioid component of the ethylketocyclazocine (EKC) discriminative stimulus in the rat

The opioid receptor selectivity of the EKC discriminative stimulus was characterized in Fischer rats trained to discriminate 0.3 mg/kg EKC (SC) from saline in a two-choice discrete-trial avoidance paradigm. The putative kappa-opioid receptor agonists EKC and U50,488H completely generalized with the EKC cue at doses of 0.3 and 10 mg/kg, respectively. The putative mu-opioid receptor agonists morphine (M) and fentanyl also dose-dependently generalized with the EKC stimulus. The generalization of M with EKC was not symmetrical, EKC and U50,488H produced little or no M-appropriate responding in rats trained to discriminate 3.0 mg/kg M (SC) from saline. This generalization pattern may reflect a lack of opioid receptor selectivity of the EKC stimulus. However, distinct mu-opioid and kappa-opioid components of the EKC cue could be identified using graded doses of naloxone in EKC-trained rats. The discriminative effects of morphine and fentanyl were blocked completely by doses of 0.1-1.0 mg/kg naloxone, whereas doses of naloxone 3-10 times greater were necessary to block the discriminative effects of EKC and U50,488H. These results suggest that EKC produces a complex discriminative stimulus with mu-opioid and kappa-opioid components that can be separated using antagonists such as naloxone.