Fernando Cano

Presentation Title

Towards an understanding of the neurobiology of incubated craving

Abstract

Drug-associated cues can induce drug craving which intensifies (incubates) during protracted withdrawal in humans and increases the risk for relapse. Animal models for different drugs of abuse, sucrose, saccharin, and food report similar molecular outcome measures – prompting the possibility that the incubation phenomenon may be mediated by common biomolecular neuroadaptations. Herein, we examined the sex-differences in sucrose-seeking behavior of Sprague Dawley rats as well as the incubation-related changes in protein expression levels of Prelimbic (PL) and Infralimbic (IL) subregions of the ventromedial prefrontal cortex (vmPFC). Rats were trained in operant chambers to press for delivery of sucrose pellets, paired with a light + tone stimuli, for 6-h sessions over 10 consecutive days and then subjected to a withdrawal day 1 or 30 (WD1 or WD30). Following withdrawal days, we conducted a 2-h test to measure cue-elicited responding (Cue Test) and observed the incubation of sucrose craving in both male and female rats: WD30 groups displayed more cue-elicited responding than WD1 groups. Subsequent immunoblot studies were conducted to probe for biomolecular changes: for females, we detected a time-dependent decrease in PL p-Akt levels, whereas for males, we detected time-dependent increases in IL mGluR5, p-Akt and p-mTOR expression/activity levels. The results observed in this incubation of sucrose craving study are opposite from those previously observed in the incubation of cocaine craving which suggests differential roles between these vmPFC subregions, such that incubation-related glutamatergic changes in the PL and IL drive cocaine- vs sucrose-seeking behavior, respectively.