RT Journal Article
SR Electronic
T1 Group I mGluR Activation Reverses Cocaine-Induced Accumulation of Calcium-Permeable AMPA Receptors in Nucleus Accumbens Synapses via a Protein Kinase C-Dependent Mechanism
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 14536
OP 14541
DO 10.1523/JNEUROSCI.3625-11.2011
VO 31
IS 41
A1 James E. McCutcheon
A1 Jessica A. Loweth
A1 Kerstin A. Ford
A1 Michela Marinelli
A1 Marina E. Wolf
A1 Kuei Y. Tseng
YR 2011
UL http://www.jneurosci.org/content/31/41/14536.abstract
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.