Stereotypy and striatal dopamine receptor changes with 1-alpha-acetylmethadol (LAAM)

Narcotics like morphine and methadone produce effects on striatal dopaminergic mechanisms as evidenced by changes in a stereotyped behavior induced by apomorphine and binding or radioactive ligands to dopamine (DA) receptors. LAAM may replace methadone in the treatment of narcotic addiction. We investigated the effect of LAAM on apomorphine induced stereotypy and the binding of 3H-spiroperidol to dopamine receptors isolated from mouse and guinea pig striata. Chronic LAAM treatment produced a behavioral supersensitivity to apomorphine. The biochemical expression of the behavioral effect was a significant increase in the number of dopamine receptor binding sits in mouse and guinea pig striata. These effects can be due to either a direct chronic blockade or postsynaptic dopamine receptors or stimulation of a presynaptic receptor which acts to reduce the amount of dopamine released during nerve activity. Work is in progress to determine the mechanism of this effect.