Pyramidal neurons in the medial prefrontal cortex (mPFC) critically contribute to cocaine-seeking behavior in humans and rodents. Activity of these neurons is significantly modulated by GABAergic, parvalbumin-containing, fast-spiking interneurons, the majority of which are enveloped by specialized structures of extracellular matrix called perineuronal nets (PNNs), which are integral to the maintenance of many types of plasticity. Using a conditioned place preference (CPP) procedure, we found that removal of PNNs primarily from the prelimbic region of the mPFC of adult, male, Sprague Dawley rats impaired the acquisition and reconsolidation of a cocaine-induced CPP memory. This impairment was accompanied by a decrease in the number of c-Fos-positive cells surrounded by PNNs. Following removal of PNNs, the frequency of inhibitory currents in mPFC pyramidal neurons was decreased; but following cocaine-induced CPP, both frequency and amplitude of inhibitory currents were decreased. Our findings suggest that cocaine-induced plasticity is impaired by removal of prelimbic mPFC PNNs and that PNNs may be a therapeutic target for disruption of cocaine CPP memories.
Urges to consume food can be driven by stimuli in the environment that are associated with previous food experience. Identifying adaptations within brain reward circuits that facilitate cue-induced food seeking is critical for understanding and preventing the overconsumption of food and subsequent weight gain. Utilizing electrophysiological, biochemical, and DiI labeling, we examined functional and structural changes in the nucleus accumbens (NAc) and prefrontal cortex (PFC) associated with time-dependent increases in food craving ('incubation of craving'). Rats self-administered 60% high fat or chow 45 mg pellets and were then tested for incubation of craving either 1 or 30 days after training. High fat was chosen for comparison to determine whether palatability differentially affected incubation and/or plasticity. Rats showed robust incubation of craving for both food rewards, although responding for cues previously associated with high fat was greater than chow at both 1 and 30 days. In addition, previous experience with high-fat consumption reduced dendritic spine density in the PFC at both time points. In contrast, incubation was associated with an increase in NAc spine density and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated transmission at 30 days in both groups. Finally, incubation of craving for chow and high fat was accompanied by an increase in calcium-permeable and calcium-impermeable AMPARs, respectively. Our results suggest that incubation of food craving alters brain reward circuitry and macronutrient composition specifically induces cortical changes in a way that may facilitate maladaptive food-seeking behaviors.
Cues previously paired with rewarding stimuli induce a time-dependent increase in the motivational craving state (incubation of craving). Whether there is an increase in craving for high-fat (HF) food over time, which may contribute to overeating and obesity, has not been determined. We hypothesized that cues paired with HF pellets would elicit a greater incubation of craving effect than those paired with standard chow (SC) pellets. Rats exposed to cues associated with either HF or SC pellets demonstrated equivalent levels of craving over an abstinence period of 30 days. Diet preference tests between SC pellets and LabDiet revealed that SC pellets were preferred over LabDiet. Rats reared on SC pellets exclusively, did not display incubation of craving for SC pellets, suggesting that prior history with the food plays an important role in cue-induced seeking behavior. Results identified cues previously associated with food undergo a comparable magnitude of incubation of craving. When ingestive behavior was measured after 30 days of abstinence, rats significantly increased their consumption of HF pellets. Our results indicate that food cues gain importance over time, trigger increased approach behaviors, and increased consumption of HF food following abstinence. This may contribute to overeating and the development of obesity.
A key factor in the development of obesity is the overconsumption of food calorically high in fat. Overconsumption of food high in fat not only promotes weight gain but elicits changes in reward processing. No studies to date have examined whether consumption of a high-fat (HF) diet alters structural plasticity in brain areas critical for reward processing, which may account for persistent changes in behavior and psychological function by reorganizing synaptic connectivity. To test whether dietary fat may induce structural plasticity we placed rats on one of three dietary conditions: ad libitum standard chow (SC), ad libitum 60% HF (HF-AL), or calorically matched 60% HF (HF-CM) for 3 weeks and then quantified dendritic spine density and type on basal and apical dendrites of pyramidal cells in layer V of the medial prefrontal cortex (mPFC) and medium spiny neurons (MSNs) of the nucleus accumbens. Our results demonstrate a significant reduction in the density of thin spines on the apical and basal segments of dendrites within the infralimbic, but not prelimbic, mPFC.
Highlights d CART is a molecular signal that encodes caloric information for meal termination d Vagal CART synthesis is blunted in obesity partly due to reduced sensitivity to CCK d Knockdown of vagal sensory CART increases food intake by preventing negative feedback d NTS administration of CART inhibits food intake in both lean and obese rats
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