PT  - JOURNAL ARTICLE
AU  - James E. McCutcheon
AU  - Jessica A. Loweth
AU  - Kerstin A. Ford
AU  - Michela Marinelli
AU  - Marina E. Wolf
AU  - Kuei Y. Tseng
TI  - Group I mGluR Activation Reverses Cocaine-Induced Accumulation of Calcium-Permeable AMPA Receptors in Nucleus Accumbens Synapses via a Protein Kinase C-Dependent Mechanism
AID  - 10.1523/JNEUROSCI.3625-11.2011
DP  - 2011 Oct 12
TA  - The Journal of Neuroscience
PG  - 14536--14541
VI  - 31
IP  - 41
4099  - http://www.jneurosci.org/content/31/41/14536.short
4100  - http://www.jneurosci.org/content/31/41/14536.full
SO  - J. Neurosci.2011 Oct 12; 31
AB  - Following prolonged withdrawal from extended access cocaine self-administration in adult rats, high conductance Ca2+-permeable AMPA receptors (CP-AMPARs) accumulate in nucleus accumbens (NAc) synapses and mediate the expression of “incubated” cue-induced cocaine craving. Using patch-clamp recordings from NAc slices prepared after extended access cocaine self-administration and >45 d of withdrawal, we found that group I metabotropic glutamate receptor (mGluR) stimulation using 3,5-dihydroxyphenylglycine (DHPG; 50 μm) rapidly eliminates the postsynaptic CP-AMPAR contribution to NAc synaptic transmission. This is accompanied by facilitation of Ca2+-impermeable AMPAR (CI-AMPAR)-mediated transmission, suggesting that DHPG may promote an exchange between CP-AMPARs and CI-AMPARs. In saline controls, DHPG also reduced excitatory transmission but this occurred through a CB1 receptor-dependent presynaptic mechanism rather than an effect on postsynaptic AMPARs. Blockade of CB1 receptors had no significant effect on the alterations in AMPAR transmission produced by DHPG in the cocaine group. Interestingly, the effect of DHPG in the cocaine group was mediated by mGluR1 whereas its effect in the saline group was mediated by mGluR5. These results indicate that regulation of synaptic transmission in the NAc is profoundly altered after extended access cocaine self-administration and prolonged withdrawal. Furthermore, they suggest that activation of mGluR1 may represent a potential strategy for reducing cue-induced cocaine craving in abstinent cocaine addicts.