Varenicline rescues nicotine-induced decrease in motivation for sucrose reinforcement

Varenicline is one of the top medications used for smoking cessation and is often prescribed before termination of nicotine use. The effect of this combined nicotine and varenicline use on the reward system and motivation for primary reinforcement is underexplored. The goal of this study was to assess the effects of nicotine and varenicline on the consumption of sucrose. In Experiment 1, we first assessed the responding for sucrose after pretreatment with nicotine (0, 0.1, or 0.4 mg/kg) and varenicline (0.0, 0.1, 1.0 mg/kg) using a behavioral economics approach. The responding for sucrose was then assessed using a progressive ratio schedule of reinforcement after pretreatment with all possible combinations of nicotine and varenicline doses. In Experiment 2, rats were assessed for the consumption of sucrose in home cages after pretreatment with nicotine and varenicline. We found that a) nicotine decreased economic demand for sucrose, b) varenicline rescued nicotine-induced reduction in economic demand for sucrose, and c) history of varenicline treatment predicted responding for sucrose on a progressive ratio schedule of reinforcement where rats with a history of varenicline treatment responded significantly lower for sucrose across nicotine doses than rats that have not being exposed to varenicline. The results of Experiment 2 largely confirmed that nicotine decreases motivation for sucrose using a passive consumption protocol and that varenicline rescues this effect. Overall, these findings suggest that varenicline interacts with the effects of nicotine by restoring nicotine-induced reduction in motivation for appetitive rewards.

Lateral septum growth hormone secretagogue receptor affects food intake and motivation for sucrose reinforcement

The hormone ghrelin promotes eating and is widely considered to be a hunger signal. Ghrelin receptors, growth hormone secretagogue receptors (GHSRs), are found in a number of specific regions throughout the brain, including the lateral septum (LS), an area not traditionally associated with the control of feeding. Here we investigated whether GHSRs in the LS play a role in the control of food intake. We examined the feeding effects of ghrelin and the GHSR antagonists ([d-Lys3]-growth hormone-releasing peptide-6 and JMV-2959) at doses subthreshold for effect when delivered to the lateral ventricle. Intra-LS ghrelin significantly increased chow intake during the midlight phase, suggesting that pharmacological activation of LS GHSRs promotes feeding. Conversely, GHSR antagonist delivered to the LS shortly before dark onset significantly reduced chow intake. These data support the hypothesis that exogenous and endogenous stimulation of GHSRs in the LS influence feeding. Ghrelin is known to affect motivation for food, and the dorsal subdivision of LS (dLS) has been shown to play a role in motivation. Thus, we investigated the role of dLS GHSRs in motivation for food reward by examining operant responding for sucrose on a progressive ratio (PR) schedule. Intra-dLS ghrelin increased PR responding for sucrose, whereas blockade of LS GHSRs did not affect responding in either a fed or fasted state. Together these findings for the first time substantiate the LS as a site of action for ghrelin signaling in the control of food intake.

Reinforcement of a reinforcing behaviour: Effect of sucrose concentration on wheel-running rate

Wheel running, unlike typical operant behavior, generates its own automatic reinforcement that alters the control exerted by extrinsic reinforcement on wheel running. The current study investigated the implications of the automatic reinforcement of wheel running by arranging different sucrose concentrations as extrinsic reinforcement for operant wheel running in ad-lib fed and food-deprived rats. Eleven female Long Evans rats ran on fixed revolution 30 schedules that delivered a drop of sucrose solution as reinforcement. Sucrose concentration varied across values of 0%, 2.5%, 5%, 10%, and 15% sucrose (w/v). Results showed that under ad-lib feeding, only the highest concentrations increased operant wheel-running rate. By contrast, under deprivation, all concentrations of sucrose increased the rate of wheel running. Despite the differences in sucrose-reinforced operant wheel-running rates by deprivation level (ad lib vs. deprived), wheel-running rates did not differ at the highest concentrations. Prior research on operant lever pressing, a response generating low (or no) automatic reinforcement, has shown considerably higher lever-pressing rates as a function of increasing amounts of sucrose reinforcement when rats are food deprived. Together, these previous observations and the current study suggest that automatic reinforcement generated by an operant decreases the control exerted by extrinsic reinforcement. Additionally, the regulation by extrinsic reinforcement on automatically reinforcing behavior depends on the organism’s motivation or deprivation level (ad lib vs. deprived).