کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8517533 | 1556589 | 2018 | 28 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Endogenous glutamate within the prelimbic and infralimbic cortices regulates the incubation of cocaine-seeking in rats
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 128, January 2018, Pages 293-300
Journal: Neuropharmacology - Volume 128, January 2018, Pages 293-300
نویسندگان
Christina B. Shin, Taylor J. Templeton, Alvin S. Chiu, Jennifer Kim, Ellen S. Gable, Philip A. Vieira, Tod E. Kippin, Karen K. Szumlinski,