Oral self-administration of N-allylnormetazocine (SKF-10,047) stereoisomers in rhesus monkeys: substitution during phencyclidine self-administration and withdrawal

Orally-delivered N-allylnormetazocine (NANM) and its isomers were tested for their ability to function as reinforcers by substituting them for phencyclidine (PCP). Two monkeys were trained to self-administer PCP (0.25 mg/ml) and water under concurrent fixed-ratio (FR) 16 schedules during 3-hr sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking devices. When the dextro (+)-isomer of NANM (0.062-1 mg/ml) was substituted for PCP, response rates increased and then decreased in an inverted U-shaped concentration-response function with peak response rates comparable to those maintained by PCP. Drug intake ranged from 2.8 to 25.7 mg/kg across the two monkeys and five concentrations. Water-maintained responding was considerably lower than drug-maintained behavior indicating that NANM was functioning as a reinforcer. As previously reported for PCP, almost all of the (+)-NANM was self-administered during the first half of the session. Substitution of the levo (-)-isomer of NANM resulted in an immediate decline to low response rates that were not distinguishable from those maintained by water. The racemic form (±) of NANM was also not self-administered in excess of concurrent water. In the second experiment concurrent PCP- and water-maintained responding were reestablished under FR 8 schedules during three 6.5-hr sessions daily. Food (6 g/pellet) was available under FR 64 and FR 80 schedules during three 1-hr sessions immediately preceding the liquid components. Water was then substituted for PCP for four days and PCP, (+)-, (-)- or (±)-NANM were reistated in subsequent replications of the experiment. During PCP withdrawal food-maintained responding was substantially disrupted, especially during the first two days. Reinstatement of PCP or (+)-NANM resulted in a rapid recovery of food maintained behavior, and the number of (+)-NANM deliveries was comparable to the baseline PCP deliveries. Food- and drug-maintained responding did not reliably recover when (-)- or (±)-NANM was introduced after four days of water substitution. However, after 5 days when (-)- or (±)-NANM was replaced by PCP, food and liquid-maintained responding immediately returned to baseline rates. These results agree with previous findings from intravenous self-administration studies that only the dextro (+)-isomer of NANM functions as a reinforcer. Neither taste factors nor PCP withdrawal altered these reinforcing effects.