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Projections from the nucleus accumbens to the ventral pallidum (VP) regulate relapse in animal models of addiction. The VP contains GABAergic (VP) and glutamatergic (VP) neurons, and a subpopulation of GABAergic neurons co-express enkephalin (VP). Rabies tracing reveals that VP and VP neurons receive preferential innervation from upstream D1- relative to D2-expressing accumbens neurons. Chemogenetic stimulation of VP neurons inhibits, whereas stimulation of VP and VP neurons potentiates cocaine seeking in mice withdrawn from intravenous cocaine self-administration. Calcium imaging reveals cell type-specific activity patterns when animals learn to suppress drug seeking during extinction training versus engaging in cue-induced cocaine seeking. During cued seeking, VP neurons increase their overall activity, and VP neurons are selectively activated around nose pokes for cocaine. In contrast, VP neurons increase their spike rate following extinction training. These data show that VP subpopulations differentially encode and regulate cocaine seeking, with VP and VP neurons facilitating and VP neurons inhibiting cocaine seeking.
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http://dx.doi.org/10.1016/j.celrep.2020.01.023 | DOI Listing |
Neuropsychopharmacology
December 2024
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
The accumulation of GluA2-lacking Ca-permeable AMPARs (CP-AMPARs) in the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) is required for the expression of incubation of cocaine craving. The exchange protein directly activated by cAMP (Epac) is an intracellular effector of cAMP and a guanine nucleotide exchange factor for the small GTPase Rap1. Epac2 has been implicated in the trafficking of AMPA receptors at central synapses.
View Article and Find Full Text PDFBiol Psychiatry Cogn Neurosci Neuroimaging
December 2024
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC; Department of Neurosciences, Medical University of South Carolina, Charleston, SC; Department of Translational Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC.
Background: Cue-induced craving precipitates relapse in drug and alcohol use disorders. Theta burst stimulation (TBS) to the left frontal pole of the medial prefrontal cortex (MPFC) has previously been shown to reduce drinking and brain reactivity to alcohol cues. This randomized, double-blind, sham-controlled target-engagement study aimed to assess whether TBS has similar effects in individuals with cocaine use disorder (CUD).
View Article and Find Full Text PDFPsychopharmacology (Berl)
December 2024
Department of Population Health Sciences, Unit of Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Rationale: Substance use disorder (SUD) is a chronic relapsing brain disorder that is characterised by loss of control over substance use. A variety of rodent models employing punishment setups have been developed to assess loss of control over substance use, i.e.
View Article and Find Full Text PDFAbstinence from cocaine use has been shown to elicit a progressive intensification or incubation of cocaine craving/seeking that is posited to contribute to propensity for relapse. While the mechanisms underlying incubation of cocaine seeking remain elusive, considerable evidence suggests that abstinence from cocaine promotes mesolimbic dopamine adaptations that contribute to exaggerated cocaine seeking. Consequently, preventing these dopamine adaptations may reduce incubation of cocaine seeking and thereby reduce the likelihood of relapse.
View Article and Find Full Text PDFPharmacol Biochem Behav
November 2024
Division on Substance Use Disorders, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Irving Medical Center, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA.
Individuals seeking treatment for their cocaine use often report depressive systems and nearly half meet criteria for major depressive disorder (MDD). This descriptive study aimed to assess the effects of the antidepressant venlafaxine alone and in combination with gabapentin on depressive symptoms, subjective effects of cocaine, and cocaine self-administration in depressed and non-depressed people who use cocaine. The effects of medication condition on mood and on the effects of smoked cocaine were compared between a group of clinically depressed people who use cocaine (n = 5) and a control group of non-depressed people who use cocaine (n = 5) using laboratory-based measures.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!