Effects of morphine, ethylketocyclazocine, and N-allylnormetazocine on classical conditioning of the rabbit nictitating membrane response.

The rabbit's nictitating membrane response was classically conditioned to tone and light conditioned stimuli presented for 800 ms before delivery of a 100-ms unconditioned shock stimulus. Both the mu receptor agonist morphine (5 mg/kg) and the kappa receptor agonist ethylketocyclazocine (1 mg/kg) significantly retarded the acquisition of conditioned responses (CRs). The retardant effects of both morphine and ethylketocyclazocine on CR acquisition could still be detected when the rabbits were tested 5 days after cessation of drug injections. At the dose employed in this study (5 mg/kg), the sigma receptor agonist N-allylnormetazocine had no effect on acquisition. The retardant effects of morphine and ethylketocyclazocine on acquisition were significantly antagonized by both naloxone (1 mg/kg) and N-allylnormetazocine (5 mg/kg). It was suggested that mu and possibly kappa receptors are involved in the retardant effects of opiates on the acquisition of classically conditioned responses.