Cocaine Self-Administration Elevates GluN2B within dmPFC Mediating Heightened Cue-Elicited Operant Responding
| Autor: | Matan Cohen, Karen K. Szumlinski, Osnat Ben-Shahar, Melissa G. Wroten, Bailey W. Miller, Arianne D. Sacramento, Tod E. Kippin |
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| Rok vydání: | 2016 |
| Předmět: |
Drug Abuse (NIDA Only)
Context (language use) Craving Pharmacology Prefrontal cortex Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cocaine Behavioral and Social Science Ifenprodil medicine 030304 developmental biology 0303 health sciences Neurosciences Substance Abuse Extinction (psychology) NMDA receptor Brain Disorders chemistry Cue reactivity 6.1 Pharmaceuticals Mental health Incubation medicine.symptom Psychology Self-administration Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of drug abuse Journal of drug abuse, vol 2, iss 2 Szumlinski, KK; Wroten, MG; Miller, BW; Sacramento, AD; Cohen, M; Ben-Shahar, O; et al.(2016). Cocaine Self-Administration Elevates GluN2B within dmPFC Mediating Heightened Cue-Elicited Operant Responding.. Journal of drug abuse, 2(2). UC Santa Barbara: Retrieved from: http://www.escholarship.org/uc/item/86h3b0mb |
| ISSN: | 2471-853X |
| Popis: | Cue-elicited drug-craving correlates with hyperactivity within prefrontal cortex (PFC), which is theorized to result from dysregulated excitatory neurotransmission. The NMDA glutamate receptor is highly implicated in addiction-related neuroplasticity. As NMDA receptor function is regulated critically by its GluN2 subunits, herein, we assayed the relation between incubated cue-elicited cocaine-seeking following extended access to intravenous cocaine (6 h/d; 0.25 mg/infusion for 10 d) and the expression of GluN2A/B receptor subunits within PFC sub regions during early versus late withdrawal (respectively, 3 vs. 30 days). Cocaine-seeking rats exhibited elevated GluN2B expression within the dorsomedial aspect of the PFC (dmPFC); this effect was apparent at both 3 and 30 days withdrawal and occurred in cocaine-experienced rats, regardless of experiencing an extinction test or not. Thus, elevated dmPFC GluN2B expression appears to reflect a pharmacodynamic response to excessive cocaine intake that is independent of the duration of drug withdrawal or re-exposure to drug-taking context. The functional relevance of elevated dmPFC GluN2B expression for drug-seeking was assessed by the local infusion of the prototypical GluN2B-selective antagonist ifenprodil (1.0 µg/side). Ifenprodil did not alter cue-elicited responding in animals with a history of saline self-administration. In contrast, ifenprodil lowered cue-elicited cocaine-seeking, while potentiating cue-elicited sucrose-seeking. Thus, the effects of an intra-dmPFC ifenprodil infusion upon cue reactivity are reinforcer-specific, arguing in favor of targeting GluN2B-containing NMDA receptors as a pharmacological strategy for reducing behavioral reactivity to drug-associated cues with the potential benefit of heightening the reinforcing properties of cues associated with non-drug primary rewards. |
| Databáze: | OpenAIRE |
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