Self administration of cocaine in monkeys receiving LAAM acutely or chronically

Abstract

Polydrug abuse remains a common problem among opioid abusers as well as patients in opioid maintenance programs. Although cocaine abuse has been reported in patients receiving methadone, the incidence of cocaine use in patients receiving l-alpha-acetylmethadol (LAAM) has not been well established. The goal of this study was to determine whether acute or chronic administration of LAAM modified the reinforcing effects of cocaine using a self-administration procedure in rhesus monkeys. Four monkeys responded under a fixed ratio (FR) 30 schedule to receive i.v. infusions of cocaine (0.0032-0.32 mg/kg/infusion) in the absence of other treatment, after acute LAAM administration (0.1-1.0 mg/kg, s.c.), and during daily administration of 1.0 mg/kg of LAAM. Cocaine maintained self-administration responding that exceeded responding maintained by saline; acutely administered LAAM had small and variable effects on self administration of cocaine. Daily LAAM administration increased the number of infusions received of at least one dose of cocaine. These studies indicated that LAAM administration did not attenuate the reinforcing effects of cocaine, suggesting that LAAM would not likely alter cocaine abuse in patients undergoing treatment for opioid abuse.

Figure 1

Self administration of cocaine (n=3) in the absence and presence of LAAM administered acutely 90 min before sessions (0.1, 0.32 or 1.0 mg/kg administered s.c.). The number of infusions received in the 90-min session (ordinate) is plotted as function of unit dose of drug (abscissae) expressed in mg/kg/infusion. Closed symbols represent the average of 10 (saline) or 9 (cocaine) determinations for each dose in each monkey (95% CL); data points without error bars indicate an instance in which the 95% CL is encompassed by the symbol. Open symbols represent data from a single session that was preceded by administration of LAAM. Each panel represents effects obtained in individual monkeys. S=saline. *=the 95% CL of number of cocaine infusions does not overlap with the 95% CL of the number of saline infusions in otherwise untreated monkeys.

Figure 2

Number of infusions of 0.032 mg/kg of cocaine received during the first and third weeks of daily treatment with 1.0 mg/kg of LAAM. Each symbol represents effects obtained in individual monkeys; data from 5 sessions were averaged to obtain each point. Error bars indicate 95% CL. Abscissa: week of LAAM treatment. See Figure 1 for other details.

Figure 3

Self administration of cocaine (n=4) determined before and during the second and fourth weeks of daily treatment with 1 mg/kg/day of LAAM administered 2 hr after sessions. See Figure 1 for other details.