Description:
<jats:p>Relapse to drug‐taking is a reoccurring phenomenon impairing addiction recovery that can be triggered by the elicitation of intense drug craving upon re‐exposure to drug‐paired cues. Cue‐elicited drug‐craving increases in a time‐dependent manner during drug abstinence ‐a phenomenon termed “incubation of craving”. The neural substrates of this phenomenon are not fully understood but are thought to involve glutamate mechanisms in the ventromedial prefrontal cortex (vmPFC) as the capacity of cocaine‐paired cues to increase glutamate release within vmPFC incubates during protracted withdrawal in concert with behavior. We hypothesize that incubated cue‐elicited glutamate release within vmPFC might drive incubated behavior. To test this hypothesis, male Sprague‐Dawley rats were trained to lever‐press for cocaine (0.25 mg/infusion; 6 h/day) for 10 consecutive days. At 30 days withdrawal, animals were infused intra‐vmPFC (0.5 μl /side) with either vehicle or 50μM of the mGlu2/3 autoreceptor agonist APDC and underwent a 30‐min test for cue‐elicited cocaine‐seeking. A control group was infused with vehicle at 3 days withdrawal to provide a base‐line response. Vehicle‐infused animals exhibited a time‐dependent intensification of cue‐reinforced responding, indicating incubation. However, the magnitude of this incubation was not influenced by 50μM APDC. As mGlu2/3 receptor down‐regulation is reported within the medial PFC of rats withdrawn from non‐contingent cocaine treatment, current studies seek to characterize mGlu2/3 expression within the vmPFC following a history of excessive cocaine intake to better understand the molecular mechanism(s) underpinning the cue hyper‐reactivity of vmPFC glutamate that presumably drives incubated cocaine‐seeking.</jats:p>