Effects of levo-alpha-acetylmethadol (LAAM) on morphine self-administration in the rat

Rats bearing cerebrocortical electrodes for recording the electroencephalogram (EEG) were rendered tolerant to and physically dependent on morphine and subsequently trained to self-administer morphine (10 mg/kg injection) through a chronic intravenous cannula. Morphine was available for self-administration 24 h/day. Once morphine intake had stabilized (10-12 injections/day), levo-alpha-acetylmethadol (LAAM) was administered noncontingently via a chronic intragastric (IG) cannula as a single daily dose of either 1 or 4 mg/kg. These morphine self-administering rats were maintained on daily LAAM treatment for 12 consecutive days. Analysis of the patterns of lever pressing, morphine self-injections, and sleep-awake behavior revealed that daily IG administration of LAAM effectively suppressed morphine self-administration. The 1 mg/kg dose of LAAM reduced morphine intake by 30%-50%, while 4 mg/kg produced an 80%-90% decrease. The reduction in morphine self-administration occurred in the absence of overt signs of narcotic withdrawal, behavioral toxicity, or disruption of sleep-awake behavior in these rats. Termination of LAAM maintenance resulted in a gradual return of level pressing and morphine intake to pre-LAAM levels.