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.
Gaiardi
Margherita
M
Department of Pharmacology, University of Bologna, Bologna, Italy. margherita.gaiardi@unibo.it
Colantoni
Alessia
A
De Luca
Valentina
V
Bartoletti
Maria
M
D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003523:Cycloserine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000963:Antimetabolites; D000697:Central Nervous System Stimulants; D003523:Cycloserine; D000661:Amphetamine