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Neuron. 2017 Dec 6;96(5):1112-1126.e5. doi: 10.1016/j.neuron.2017.11.012.

Endocannabinoid Actions on Cortical Terminals Orchestrate Local Modulation of Dopamine Release in the Nucleus Accumbens.

Author information

1
Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Rockville, MD, USA.
2
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
3
Neuronal Networks Section, National Institute on Drug Abuse, US National Institutes of Health, Baltimore, MD, USA.
4
Department of Biochemistry and Molecular Biology I, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) and Instituto Universitario de Investigación Neuroquímica (IUIN), Complutense University, Madrid, Spain.
5
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: jcheer@som.umaryland.edu.
6
Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Rockville, MD, USA. Electronic address: lovindav@mail.nih.gov.

Abstract

Dopamine (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.

KEYWORDS:

AMPA receptors; CB1 receptors; Endocannabinoids; acetylcholine; dopamine; glutamate; prefrontal cortex; reward; voltammetry

PMID:
29216450
PMCID:
PMC5728656
DOI:
10.1016/j.neuron.2017.11.012
[Indexed for MEDLINE]
Free PMC Article

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