Bidirectional effects of inhibiting or potentiating NMDA receptors on extinction after cocaine self-administration in rats. Psychopharmacology (Berl) 2014 Dec;231(24):4585-94
Date
05/23/2014Pubmed ID
24847958Pubmed Central ID
PMC4233003DOI
10.1007/s00213-014-3607-1Scopus ID
2-s2.0-84939891929 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
RATIONALE: Extinction of drug seeking is facilitated by NMDA receptor (NMDAr) agonists, but it remains unclear whether extinction is dependent on NMDAr activity.
OBJECTIVES: We investigated the necessity of NMDArs for extinction of cocaine seeking and whether extinction altered NMDAr expression within extinction-related neuroanatomical loci.
METHODS: Rats were trained to lever press for i.v. infusions of cocaine or sucrose reinforcement prior to extinction training or withdrawal.
RESULTS: Administration of the NMDAr competitive antagonist CPP prior to four brief extinction sessions impaired subsequent extinction retention. In contrast, administration of the NMDAr coagonist D-serine after four brief extinction sessions attenuated lever pressing during subsequent extinction, indicative of facilitated consolidation of extinction. Furthermore, expression of the NMDAr subunits, GluN2A and GluN2B, was not altered in the ventromedial prefrontal cortex. However, both GluN2A and GluN2B subunit expression in the nucleus accumbens increased following cocaine self-administration, and this increased expression was relatively resistant to modulation by extinction.
CONCLUSIONS: Our findings demonstrate that extinction of cocaine seeking is bidirectionally mediated by NMDArs and suggest that selective modulation of NMDAr activity could facilitate extinction-based therapies for treatment of cocaine abuse.
Author List
Hafenbreidel M, Rafa Todd C, Twining RC, Tuscher JJ, Mueller DAuthor
Jennifer J. Tuscher PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCocaine
Cocaine-Related Disorders
Dopamine Uptake Inhibitors
Drug-Seeking Behavior
Excitatory Amino Acid Antagonists
Extinction, Psychological
Male
Nucleus Accumbens
Piperazines
Rats
Rats, Long-Evans
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate
Self Administration
