PT  - JOURNAL ARTICLE
AU  - Fourgeaud, Lawrence
AU  - Mato, Susana
AU  - Bouchet, Delphine
AU  - Hémar, Agnès
AU  - Worley, Paul F.
AU  - Manzoni, Olivier J.
TI  - A Single &lt;em&gt;In Vivo&lt;/em&gt; Exposure to Cocaine Abolishes Endocannabinoid-Mediated Long-Term Depression in the Nucleus Accumbens
AID  - 10.1523/JNEUROSCI.0671-04.2004
DP  - 2004 Aug 04
TA  - The Journal of Neuroscience
PG  - 6939--6945
VI  - 24
IP  - 31
4099  - http://www.jneurosci.org/content/24/31/6939.short
4100  - http://www.jneurosci.org/content/24/31/6939.full
SO  - J. Neurosci.2004 Aug 04; 24
AB  - In the nucleus accumbens (NAc), a key structure to the effects of all addictive drugs, presynaptic cannabinoid CB1 receptors (CB1Rs) and postsynaptic metabotropic glutamate 5 receptors (mGluR5s) are the principal effectors of endocannabinoid (eCB)-mediated retrograde long-term depression (LTD) (eCB-LTD) at the prefrontal cortex-NAc synapses. Both CB1R and mGluR5 are involved in cocaine-related behaviors; however, the impact of in vivo cocaine exposure on eCB-mediated retrograde synaptic plasticity remains unknown. Electrophysiological and biochemical approaches were used, and we report that a single in vivo cocaine administration abolishes eCB-LTD. This effect of cocaine was not present in D1 dopamine receptor (D1R) -/- mice and was prevented when cocaine was coadministered with the selective D1R antagonist 8-chloro-2,3,4,5-tetrahydro-3-5-1h-3-benzazepin-7-ol (0.5 mg/kg) or with the NMDA receptor (NMDAR) blocker (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (1 mg/kg), suggesting the involvement of D1R and NMDAR. We found that the cocaine-induced blockade of retrograde signaling was correlated with enhanced expression levels of Homer scaffolding proteins containing the coiled-coil domain and accompanied by a strong reduction of mGluR5 surface expression. The results suggest that cocaine-induced loss of eCB retrograde signaling is caused by a reduction in the ability of mGluR5 to translate anterograde glutamate transmission into retrograde eCB signaling.