Individual differences in conditioned approach and cocaine‐induced locomotor activity in obesity‐susceptible rats

Abstract

The continuing obesity epidemic has increased the need to understand the neural and behavioral mechanisms that drive over‐eating. Studies in rodents and humans have shown that some individuals are more susceptible to diet‐induced weight gain than others. This may be due in part to differences in the function of mesolimbic circuits that underlie motivation. We previously found that selectively bred male obesity‐prone (OP) rats are more sensitive to the acute locomotor activating effects of cocaine compared to obesity‐resistant (OR) rats, and that intrinsic excitability of medium spiny neurons in the Nucleus Accumbens (NAc) is enhanced in OP vs. OR males. In addition, motivational responses to Pavlovian food cues mediated by activity in the NAc are stronger in OP vs. OR rats. However, little is known about potential differences in OP vs. OR females, and it's unclear whether similar neurobehavioral differences are present in outbred rats. Therefore, we evaluated conditioned approach and sensitivity to the acute locomotor‐activating effects of cocaine in outbred rats screened for sensitivity to diet‐induced obesity, as well as F1 offspring generated from these rats. During the initial screen, males had free access to high‐fat diet for 2 weeks, and females for 3 weeks. Weight and food intake were measured daily, and fat mass was determined by NMR at the end of the screening period. Based upon their total change in weight over the screening period, we designated each outbred rat a high or low gainer. F1 offspring were generated by pairing the top 4 male and female high gainers and the bottom 4 male and female low gainers prior to behavioral testing. Post‐NMR, outbred rats began chronic food restriction and underwent training for a simple Pavlovian task where we presented an auditory cue paired with 2 unflavored Bio‐serv food pellets 25 times per session for 10 sessions. Following Pavlovian training, rats underwent extinction followed by reinstatement. Finally, rats went through locomotor testing where they received increasing doses of cocaine within session (males: 7.5 mg/kg, 15 mg/kg, 30 mg/kg; females: 5 mg/kg, 10 mg/kg, 20 mg/kg, i.p.). Adult F1 offspring underwent the same behavioral training and testing as their outbred parents. Initial results suggest slight trends towards a greater magnitude of conditioned approach in high vs low gainers in males but not females. The magnitude of reinstatement was greater in both male and female high gainers vs. low gainers. Finally, both males and females identified as high gainers also trended towards greater peak and sustained acute cocaine‐induced locomotor activity than low gainers. Initial results from behavioral studies in F1 offspring from high and low gainer breeding pairs show greater conditioned approach in F1 high gainers compared to F1 low gainers. Taken together, data from screened outbred rats and their F1 offspring support the idea that susceptibility to weight gain is accompanied by enhanced motivational responses to food cues and increased responsivity of mesolimbic circuits.Support or Funding InformationThis work was supported by NIDDK R01‐DK106188, 1R01DK115526 and NIDA T32DA007268 to CRF. Studies also utilized the Chemistry Core of the Michigan Diabetes Research and Training Center funded by DK020572 awarded by NIDDK.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.