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. Author manuscript; available in PMC: 2016 Sep 29.
Published in final edited form as: Cell Rep. 2015 Sep 10;12(12):1997–2008. doi: 10.1016/j.celrep.2015.08.041

Figure 7. Putative Mechanism of Cocaine Mobilization of 2-AG and Inhibition of GABA Neurotransmission in the VTA.

Figure 7

Glutamate spillover under baseline conditions activates mGluR1s, and α1-adrenergic receptors located on VTA DA neurons are activated by NE whose clearance is prevented by cocaine blockade of the NET. This co-activation of Gq11-coupled mGluR1 and α1Rs cooperatively stimulates PLC-β leading to DAG formation. DAG is then converted to 2-AG, via DGL-α, then crosses the extracellular space through an unknown mechanism to activate CB1Rs located on GABA axon terminals. Activation of these presynaptic CB1Rs inhibits GABA release onto postsynaptic GABAB receptors, leading to 2-AG-mediated disinhibition of DA neurons. This increases DA transients in the NAc to enhance the rewarding properties of cocaine.