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

NEUROPHARMACOLOGY

卷:128

Article

Shin, Christina B.¹  Templeton, Taylor J.¹  Chiu, Alvin S.¹  Kim, Jennifer¹  Gable, Ellen S.¹  Vieira, Philip A.^3,4  Kippin, Tod E.^1,2,3  Szumlinski, Karen K.^1,2 

[1] Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA

[2] Univ Calif Santa Barbara, Neurosci Res Inst, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA

[3] Univ Calif Santa Barbara, Ctr Collaborat Biotechnol, Santa Barbara, CA 93106 USA

[4] Calif State Univ Dominguez Hills, Dept Psychol, 1000 E Victoria Ave, Carson, CA 90747 USA

关键词: Cocaine;    Incubation;    Prelimbic cortex;    Infralimbic cortex;    Glutamate;    Drug-seeking;    Craving;   

DOI  :  10.1016/j.neuropharm.2017.10.024

来源: Elsevier

【 摘 要 】

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 mu M of the excitatory amino acid transporter inhibitor threo-beta-benzyloxyaspartate (TBOA; to raise endogenous glutamate) into either the IL or PL (0.5 mu l/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. (C) 2017 Published by Elsevier Ltd.

【 授权许可】

Free