Discrimination of a Single Dose of Morphine Followed by Naltrexone: Substitution of Other Agonists for Morphine and Other Antagonists for Naltrexone in a Rat Model of Acute Dependence

Rats were trained to discriminate 4-h pretreatment with 10 mg/kg morphine and 15-min pretreatment with 0.3 mg/kg naltrexone (morphine3naltrexone) from pretreatment with saline and 0.3 mg/kg naltrexone (saline3naltrexone). The discrimination seems to derive from interoceptive stimuli from antagonist-precipitated withdrawal from acute mor-phine dependence. The purpose of this study was to extend pharmacological characterization of the discrimination by testing opioid agonists other than morphine and antagonists other than naltrexone. Of seven -opioid agonists tested in place of morphine, only two (heroin and levorphanol) substi-tuted completely for it; trials completed on the morphine3 naltrexone-appropriate lever increased as a function of ag-onist and naltrexone dose. Agonists with intrinsic efficac