N-methyl-D-aspartic acid receptors on striatal neurons are essential for cocaine cue reactivity in mice.
BACKGROUND
Environmental cues associated with cocaine evoke craving and seeking. This process, termed cue reactivity, is a critical element of cocaine addiction. Although glutamatergic neurotransmission has been implicated in this effect of cocaine, the precise subtype and localization in the brain of the glutamatergic receptor critical for cocaine cue reactivity is not well-understood.


METHODS
We used a conditional N-methyl-D-aspartic acid receptor (NMDAR) knockout mouse whose NMDAR gene was deleted by Cre expression restricted to striatal neurons. To evaluate the role of NMDAR in cocaine cue reactivity, conditional knockout mice and control mice (n = 5-8/group) were conditioned for place preference with cocaine (5 and 10 mg/kg SC) for 3 days. Their subsequent place preference was examined in a drug-free state.


RESULTS
Although control mice developed cocaine conditioned place preference, mice deficient for NMDAR on striatal neurons failed to develop conditioned place preference.


CONCLUSIONS
The NMDAR on striatal neurons is essential for the development of cocaine cue reactivity in the place conditioning paradigm. Our finding identifies a brain region whose constitutive NMDAR level serves as a determinant for susceptibility to this aspect of cocaine addiction.
Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Soh
S
Agatsuma
Mai T
MT
Dang
Yuqing
Y
Li
Noboru
N
Hiroi
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011699:Putamen / Q000166:cytology / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
D018765:Dopamine Uptake Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D003042:Cocaine