Phencyclidine-like discriminative effects of opioids in the rat

Possible commonalities in the discriminative stimulus properties of phencyclidine (PCP) and opioids were investigated in rats trained to discriminate between i.p. injections of saline and 2.0 mg/kg of PCP in a two-choice discrete-trial avoidance paradigm. Behavior was considered to be under stimulus control when a rat reliably completed at least 18 trials of a 20-trial session on the appropriate choice lever after receiving PCP or saline. Tests of stimulus generalization were performed over an 8- to 32-fold range of doses with ketamine, a PCP analog, and eight opioids. Dose- and time-dependent stimulus control of behavior comparable to that produced by 2.0 mg/kg of PCP (defined by the number of trials completed on the PCP-appropriate choice lever) were produced by ketamine and the opioids cyclazocine, SKF 10,047 and dextrorphan. These drugs also produced orderly increases in responses during the interval between trials suggestive of a relationship between this effect and PCP-like stimulus control. In contrast, after ethylketocyclazocine, ketocyclazocine, pentazocine and dextromethorphan trials were completed primarily on the saline-appropriate lever and responding between trials produced did not change. Neither the PCP-like stimulus control of behavior nor the increased responding between trials produced by cyclazocine were prevented by pretreatment with naltrexone (1.0 mg/kg). These results provide further evidence that PCP and certain opioids share a common component of action that is probably mediated by neuronal substrates not usually associated with the activity of opioids.