Premium
Deletion of the NR1 subunit of the N‐methyl‐D‐aspartate (NMDA) glutamate receptor increases operant responding for food and cocaine self‐administration
Author(s) -
Simontacchi Kelly C.,
ADykstra Linda
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a674-d
Subject(s) - nmda receptor , glutamatergic , glutamate receptor , addiction , self administration , pharmacology , neuroscience , receptor , medicine , psychology
Recent evidence suggests that glutamate plays a critical role in the acute reinforcing effects of cocaine and the neuroadaptive changes in the reward system leading to “addiction”. Accordingly, investigations on the effect of alterations in glutamatergic activity offer important insights into the neurobiological processes underlying addiction and may lead to new pharmacotherapeutic strategies for drug dependence treatment. The objective of the present study was to investigate the reinforcing effects of food and cocaine in mice with a deletion in the essential NR1 subunit of the NMDA glutamate receptor (NR1 KD) and their wildtype littermates (NR1 WT) using an operant self‐administration procedure. NR1 KD and WT mice were trained to perform a nose‐poke response for presentation of a vanilla flavored nutritional drink (Ensure®). Responding for Ensure® was evaluated across different concentrations on a fixed ratio (FR1) and progressive ratio (PR) schedule of reinforcement. Mice were then implanted with jugular catheters and nose‐poke responding resulted in an i.v. infusion of 0.3 mg/kg of cocaine. The results demonstrate that total responses were increased and breakpoints were higher in NR1 KD mice compared to WT mice across all concentrations of Ensure®, suggesting enhanced reinforcing effects of Ensure® in mice with a deletion in the NR1 gene. Total responses for cocaine were also greater in NR1 KD mice. Collectively, these data suggest that the NMDA receptor plays an important role in the modulation of the reinforcing effects of Ensure® and cocaine. Supported by F32‐DA019299 (KAC) and R01‐DA02749 (LAD).