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Article Abstract
Introduction: The incubation of craving is a behavioral phenomenon in which cue-elicited craving increases during a period of drug abstinence. Incubated cocaine-craving is associated with increased extracellular glutamate within the medial prefrontal cortex (mPFC) and this release, particularly within the prelimbic (PL) subregion, is necessary for incubated cocaine-craving. A potential candidate mediating these incubation-driving effects of glutamate release within the PL are alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.
Methods: To investigate the role of mPFC AMPA receptors (AMPARs) in incubated craving, male and female Sprague-Dawley rats were trained to self-administer cocaine for 6 h/day for 10 consecutive days. Either during early or later withdrawal, rats were infused intra-PL with the AMPA/kainate receptor antagonist NBQX (0 or 1 µg/0.5 µl per side), followed by 30-min tests for cue-induced responding. Immunoblotting was also conducted to relate the expression of incubated cocaine- and sucrose-craving to AMPAR subunit expression within mPFC subregions.
Results: Intra-PL NBQX blocked incubated craving expressed in late, but not early, withdrawal. In contrast, an intra-PL NBQX infusion increased cue-induced cocaine-seeking in female rats tested in early withdrawal. No incubation-related changes in AMPAR subunit expression were detected within the PL or IL of rats of either sex and no estrus-associated changes in subunit expression were detected in female rats exhibiting incubated cocaine-craving. In contrast, elevated GluA1 expression was observed within the IL of male rats exhibiting an incubation of sucrose-craving.
Discussion: Together, these findings indicate a necessary role for AMPAR/kainate receptors within the PL in driving incubated cocaine-craving and suggest that AMPAR/kainate receptors located within the IL may be involved also in sucrose-craving selectively in males.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391076 | PMC |
| http://dx.doi.org/10.3389/fpsyt.2025.1627477 | DOI Listing |
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