Endogenous glutamate within the prelimbic and infralimbic cortices regulates the incubation of cocaine-seeking in rats.

Autor: Shin CB; Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA., Templeton TJ; Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA., Chiu AS; Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA., Kim J; Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA., Gable ES; Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA., Vieira PA; Center for Collaborative Biotechnology, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA., Kippin TE; Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA; Department of Molecular, Cellular and Developmental Biology, Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA; Center for Collaborative Biotechnology, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA., Szumlinski KK; Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA; Department of Molecular, Cellular and Developmental Biology, Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA. Electronic address: karen.szumlinski@psych.ucsb.edu.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2018 Jan; Vol. 128, pp. 293-300. Date of Electronic Publication: 2017 Oct 20.
DOI: 10.1016/j.neuropharm.2017.10.024
Abstrakt: The incubation of cue-reinforced cocaine-seeking coincides with increased extracellular glutamate within the ventromedial prefrontal cortex (vmPFC). The vmPFC is comprised of two subregions that oppositely regulate drug-seeking, with infralimbic (IL) activity inhibiting, and prelimibic (PL) activity facilitating, drug-seeking. Thus, we hypothesized that increasing and decreasing endogenous glutamate within the IL would attenuate and potentiate, respectively, cue-reinforced drug-seeking behavior, with the converse effects observed upon manipulations of endogenous glutamate within the PL. Male Sprague-Dawley rats were trained to self-administer cocaine (0.25 mg/infusion; 6 h/day X 10 days), the delivery of which was signaled by a tone-light cue. Rats were then subdivided into 3 or 30 day withdrawal groups. For testing, rats were microinjected with vehicle, 20 mM of the mGlu2/3 agonist LY379268 (to lower endogenous glutamate), or 300 μM of the excitatory amino acid transporter inhibitor threo-β-benzyloxyaspartate (TBOA; to raise endogenous glutamate) into either the IL or PL (0.5 μl/side) and then given a 30-min test for cue-reinforced drug-seeking. Vehicle-infused rats exhibited incubated responding on the cocaine-associated lever. Neither LY379268 nor TBOA altered behavior at 3 days withdrawal, indicating that glutamate within neither subregion regulates cue-reinforced drug-seeking during early withdrawal. At 30 days withdrawal, intra-PL LY379268 microinjection significantly decreased drug-seeking behavior, while the effect was more modest when infused intra-IL. Interestingly, intra-IL TBOA attenuated incubated drug-seeking during protracted withdrawal, but did not affect behavior when infused intra-PL. These results argue that glutamate release within the PL in response to drug-seeking likely drives the manifestation of incubated cocaine-seeking during protracted withdrawal.
(Copyright © 2017. Published by Elsevier Ltd.)
Databáze: MEDLINE
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