D-cycloserine inhibits the development and the expression of locomotor sensitization to amphetamine in rats

Amphetamine use is now an epidemic of global proportions; however, no approved medications are available to treat amphetamine abusers. Since glutamate plays a crucial role in regulating the development and expression of addictive behaviors, such as sensitization, in the present study we examined the possible effect of D-cycloserine, a partial agonist at the glycine site of N-methyl-D-aspartate receptors, on the development and expression of locomotor sensitization to amphetamine. Rats were intraperitoneally injected with saline or D-cycloserine (6 mg/kg), before saline or amphetamine (1.5 mg/kg), on days 1–10. Three days after ceasing the chronic treatment, a challenge test was run. The animals received saline or 6 mg/kg D-cycloserine and, 1 h later, they received 0.75 or 1.5 mg/kg amphetamine; motility was recorded for 2 h. The chronic treatment with D-cycloserine alone had no influence on the acute behavioral response to amphetamine. However, D-cycloserine prevented the development and inhibited the expression of amphetamine sensitization; in both cases the D-cycloserine effect was not significantly different as a function of amphetamine challenge dose. As behavioral sensitization is proposed to model the enhanced ‘drug wanting’ observed in psychostimulant abusers, the present data suggest that D-cycloserine might be a useful therapeutic approach to its treatment.