Expression and acquisition of the conditioned place preference response to cocaine in rats is blocked by selective inhibitors of the enzyme N-acetylated-alpha-linked-acidic dipeptidase (NAALADASE).
In this study we examined the effect of 2-(phosphonomethyl)pentanedioic acid (2-PMPA) and GPI 5693, selective inhibitors of the enzyme N-Acetylated-alpha-Linked-Acidic Dipeptidase (NAALADase; glutamate carboxypeptidase II; EC no. 3.4.17.21), which cleaves glutamate from the dipeptide N-acetyl-aspartyl-glutamate (NAAG), on the conditioned place preference (CPP) response to cocaine in male rats. The i.p. administration of 15 mg/kg of cocaine produced a significant CPP response. The acquisition and expression of the CPP response to cocaine was blocked by the i.p. administration of 100 mg/kg of 2-PMPA and the p.o. administration of 30 mg/kg of GPI 5693. In contrast, neither 2-PMPA nor GPI 5693 produced a CPP or conditioned place aversion response when administered alone. Furthermore, neither 2-PMPA or GPI 5693 altered the expression of the CPP response to food. These results indicate that NAALADase inhibitors block the incentive motivational value of cocaine, suggesting that such agents may be of use in treating cue-induced craving in cocaine addicts.
Slusher
B S
BS
Department of Research, Guilford Pharmaceuticals, Inc., Baltimore, Maryland, USA.
Thomas
A
A
Paul
M
M
Schad
C A
CA
Ashby
C R
CR
D000818:Animals; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D043425:Glutamate Carboxypeptidase II; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
C402107:2-(phosphonomethyl)pentanedioic acid; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; D002268:Carboxypeptidases; D043425:Glutamate Carboxypeptidase II; D003042:Cocaine