Endocannabinoid Actions on Cortical Terminals Orchestrate Local Modulation of Dopamine Release in the Nucleus Accumbens
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AbstractDopamine (DA) transmission mediates numerous aspects of behavior. Although DA release is strongly linked to firing of DA neurons, recent developments indicate the importance of presynaptic modulation at striatal dopaminergic terminals. The endocannabinoid (eCB) system regulates DA release and is a canonical gatekeeper of goal-directed behavior. Here we report that extracellular DA increases induced by selective optogenetic activation of cholinergic neurons in the nucleus accumbens (NAc) are inhibited by CB1 agonists and eCBs. This modulation requires CB1 receptors on cortical glutamatergic afferents. Dopamine increases driven by optogenetic activation of prefrontal cortex (PFC) terminals in the NAc are similarly modulated by activation of these CB1 receptors. We further demonstrate that this same population of CB1 receptors modulates optical self-stimulation sustained by activation of PFC afferents in the NAc. These results establish local eCB actions on PFC terminals within the NAc that inhibit mesolimbic DA release and constrain reward-driven behavior. Mateo et al. demonstrate that glutamate and acetylcholine-driven dopamine release in the nucleus accumbens is modulated by CB1 receptors on prefrontal cortical afferents. Endogenous activation of these receptors modifies dopamine-dependent reward-driven behavior sustained by optical activation of prefrontal cortical terminals. Copyright 2017
SponsorsFunding from the Division of Intramural Clinical and Biological Research of NIAAA , ZIA AA000416, the Intramural Research Program of NIDA ZIA DA000511, the Spanish Ministerio de Economıa y Competitividad (grant number SAF2015-64945-R to M.G.), NIH grant numbers DA022340 and DA042595 and DA041827 and a Postdoctoral Research Associate (PRAT) Fellowship from NIGMS (K.A.J.).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85037626656&doi=10.1016%2fj.neuron.2017.11.012&partnerID=40&md5=5a9f069b012fe4ebef1f36c86af34cd0; http://hdl.handle.net/10713/9891