How Diet Can Alter Reward-Seeking Behavior

The epidemic of chronic, preventable diseases such as obesity and diabetes remain a serious health concern, driven largely by 1) changes in the global food supply as the consumption of nutritive foods decreases and that of highly refined and processed foods increases, and 2) a subsequent inability to limit food consumption appropriately. While obesity remains at the forefront of preventable diseases, recent evidence suggests that it is strongly associated with insulin resistance and type 2 diabetes, so much so that the phrase “diabesity” has been coined to emphasize their comorbidity. Growing evidence suggests that the foods we eat can have serious consequences not just in the periphery (e.g., weight gain), but can alter our neurochemistry and behavior as well. The experiments presented here probe this issue in two parts. First, we examine whether a junk food diet can alter the use of external and internal cues to guide reward seeking behavior. To this end, we used general and outcome-specific Pavlovian-to-instrumental transfer (PIT) tests to probe incentive motivation and decision making, respectively, and a test of outcome devaluation to examine the sensitivity of reward seeking to a decrease in outcome value, after either intermittent or ad libitum junk food exposure. We found that intermittent junk food exposure disrupts general and outcome-specific PIT, promoting reward seeking in response to cues only loosely paired with reward and inconsistent with outcomes predicted by the cue. Ad libitum junk food exposure suppresses reward seeking during a general PIT test, and disrupts outcome-specific PIT similarly to intermittent junk food exposure. Junk food exposure also disrupts the ability of internal, interoceptive cues about satiety state to adjust reward seeking in a test of outcome devaluation, irrespective of the pattern of junk food exposure.We also examined whether an insulin-disrupting high fructose diet would alter incentive motivation in a general PIT test. We used fast-scan cyclic voltammetry to examine dopamine signaling during the PIT test, and in anesthetized animals to further assess dopamine reuptake kinetics. We found that insulin resistant rats were behaviorally and neurochemically sensitive to both reward-paired and “neutral” cues, demonstrating increased reward seeking and phasic dopamine release in response to both types of cues. We also found that dopamine reuptake was prolonged in insulin resistant rats, and that treatment with the insulin receptor sensitizing drug pioglitazone normalized reuptake and incentive motivation

How Diet Can Alter Reward-Seeking Behavior

The epidemic of chronic, preventable diseases such as obesity and diabetes remain a serious health concern, driven largely by 1) changes in the global food supply as the consumption of nutritive foods decreases and that of highly refined and processed foods increases, and 2) a subsequent inability to limit food consumption appropriately. While obesity remains at the forefront of preventable diseases, recent evidence suggests that it is strongly associated with insulin resistance and type 2 diabetes, so much so that the phrase “diabesity” has been coined to emphasize their comorbidity. Growing evidence suggests that the foods we eat can have serious consequences not just in the periphery (e.g., weight gain), but can alter our neurochemistry and behavior as well. The experiments presented here probe this issue in two parts. First, we examine whether a junk food diet can alter the use of external and internal cues to guide reward seeking behavior. To this end, we used general and outcome-specific Pavlovian-to-instrumental transfer (PIT) tests to probe incentive motivation and decision making, respectively, and a test of outcome devaluation to examine the sensitivity of reward seeking to a decrease in outcome value, after either intermittent or ad libitum junk food exposure. We found that intermittent junk food exposure disrupts general and outcome-specific PIT, promoting reward seeking in response to cues only loosely paired with reward and inconsistent with outcomes predicted by the cue. Ad libitum junk food exposure suppresses reward seeking during a general PIT test, and disrupts outcome-specific PIT similarly to intermittent junk food exposure. Junk food exposure also disrupts the ability of internal, interoceptive cues about satiety state to adjust reward seeking in a test of outcome devaluation, irrespective of the pattern of junk food exposure.We also examined whether an insulin-disrupting high fructose diet would alter incentive motivation in a general PIT test. We used fast-scan cyclic voltammetry to examine dopamine signaling during the PIT test, and in anesthetized animals to further assess dopamine reuptake kinetics. We found that insulin resistant rats were behaviorally and neurochemically sensitive to both reward-paired and “neutral” cues, demonstrating increased reward seeking and phasic dopamine release in response to both types of cues. We also found that dopamine reuptake was prolonged in insulin resistant rats, and that treatment with the insulin receptor sensitizing drug pioglitazone normalized reuptake and incentive motivation

Differential effects of systemic cholinergic receptor blockade on Pavlovian incentive motivation and goal-directed action selection.

Reward-seeking actions can be guided by external cues that signal reward availability. For instance, when confronted with a stimulus that signals sugar, rats will prefer an action that produces sugar over a second action that produces grain pellets. Action selection is also sensitive to changes in the incentive value of potential rewards. Thus, rats that have been prefed a large meal of sucrose will prefer a grain-seeking action to a sucrose-seeking action. The current study investigated the dependence of these different aspects of action selection on cholinergic transmission. Hungry rats were given differential training with two unique stimulus-outcome (S1-O1 and S2-O2) and action-outcome (A1-O1 and A2-O2) contingencies during separate training phases. Rats were then given a series of Pavlovian-to-instrumental transfer tests, an assay of cue-triggered responding. Before each test, rats were injected with scopolamine (0, 0.03, or 0.1 mg/kg, intraperitoneally), a muscarinic receptor antagonist, or mecamylamine (0, 0.75, or 2.25 mg/kg, intraperitoneally), a nicotinic receptor antagonist. Although the reward-paired cues were capable of biasing action selection when rats were tested off-drug, both anticholinergic treatments were effective in disrupting this effect. During a subsequent round of outcome devaluation testing-used to assess the sensitivity of action selection to a change in reward value--we found no effect of either scopolamine or mecamylamine. These results reveal that cholinergic signaling at both muscarinic and nicotinic receptors mediates action selection based on Pavlovian reward expectations, but is not critical for flexibly selecting actions using current reward values

Phasic mesolimbic dopamine signaling encodes the facilitation of incentive motivation produced by repeated cocaine exposure

Drug addiction is marked by pathological drug seeking and intense drug craving, particularly in response to drug-related stimuli. Repeated psychostimulant administration is known to induce long-term alterations in mesolimbic dopamine (DA) signaling that are hypothesized to mediate this heightened sensitivity to environmental stimuli. However, there is little direct evidence that drug-induced alteration in mesolimbic DA function underlies this hypersensitivity to motivational cues. In the current study, we tested this hypothesis using fast-scan cyclic voltammetry to monitor phasic DA signaling in the nucleus accumbens core of cocaine-pretreated (6 once-daily injections of 15 mg/kg, i.p.) and drug-naive rats during a test of cue-evoked incentive motivation for food - the Pavlovian-to-instrumental transfer task. We found that prior cocaine exposure augmented both reward seeking and DA release triggered by the presentation of a reward-paired cue. Furthermore, cue-evoked DA signaling positively correlated with cue-evoked food seeking and was found to be a statistical mediator of this behavioral effect of cocaine. Taken together, these findings provide support for the hypothesis that repeated cocaine exposure enhances cue-evoked incentive motivation through augmented phasic mesolimbic DA signaling. This work sheds new light on a fundamental neurobiological mechanism underlying motivated behavior and its role in the expression of compulsive reward seeking. © 2014 American College of Neuropsychopharmacology

Phasic mesolimbic dopamine signaling encodes the facilitation of incentive motivation produced by repeated cocaine exposure

Drug addiction is marked by pathological drug seeking and intense drug craving, particularly in response to drug-related stimuli. Repeated psychostimulant administration is known to induce long-term alterations in mesolimbic dopamine (DA) signaling that are hypothesized to mediate this heightened sensitivity to environmental stimuli. However, there is little direct evidence that drug-induced alteration in mesolimbic DA function underlies this hypersensitivity to motivational cues. In the current study, we tested this hypothesis using fast-scan cyclic voltammetry to monitor phasic DA signaling in the nucleus accumbens core of cocaine-pretreated (6 once-daily injections of 15 mg/kg, i.p.) and drug-naive rats during a test of cue-evoked incentive motivation for food - the Pavlovian-to-instrumental transfer task. We found that prior cocaine exposure augmented both reward seeking and DA release triggered by the presentation of a reward-paired cue. Furthermore, cue-evoked DA signaling positively correlated with cue-evoked food seeking and was found to be a statistical mediator of this behavioral effect of cocaine. Taken together, these findings provide support for the hypothesis that repeated cocaine exposure enhances cue-evoked incentive motivation through augmented phasic mesolimbic DA signaling. This work sheds new light on a fundamental neurobiological mechanism underlying motivated behavior and its role in the expression of compulsive reward seeking. © 2014 American College of Neuropsychopharmacology

Phasic mesolimbic dopamine signaling encodes the facilitation of incentive motivation produced by repeated cocaine exposure.

Drug addiction is marked by pathological drug seeking and intense drug craving, particularly in response to drug-related stimuli. Repeated psychostimulant administration is known to induce long-term alterations in mesolimbic dopamine (DA) signaling that are hypothesized to mediate this heightened sensitivity to environmental stimuli. However, there is little direct evidence that drug-induced alteration in mesolimbic DA function underlies this hypersensitivity to motivational cues. In the current study, we tested this hypothesis using fast-scan cyclic voltammetry to monitor phasic DA signaling in the nucleus accumbens core of cocaine-pretreated (6 once-daily injections of 15 mg/kg, i.p.) and drug-naive rats during a test of cue-evoked incentive motivation for food-the Pavlovian-to-instrumental transfer task. We found that prior cocaine exposure augmented both reward seeking and DA release triggered by the presentation of a reward-paired cue. Furthermore, cue-evoked DA signaling positively correlated with cue-evoked food seeking and was found to be a statistical mediator of this behavioral effect of cocaine. Taken together, these findings provide support for the hypothesis that repeated cocaine exposure enhances cue-evoked incentive motivation through augmented phasic mesolimbic DA signaling. This work sheds new light on a fundamental neurobiological mechanism underlying motivated behavior and its role in the expression of compulsive reward seeking

Phasic mesolimbic dopamine signaling encodes the facilitation of incentive motivation produced by repeated cocaine exposure.

Drug addiction is marked by pathological drug seeking and intense drug craving, particularly in response to drug-related stimuli. Repeated psychostimulant administration is known to induce long-term alterations in mesolimbic dopamine (DA) signaling that are hypothesized to mediate this heightened sensitivity to environmental stimuli. However, there is little direct evidence that drug-induced alteration in mesolimbic DA function underlies this hypersensitivity to motivational cues. In the current study, we tested this hypothesis using fast-scan cyclic voltammetry to monitor phasic DA signaling in the nucleus accumbens core of cocaine-pretreated (6 once-daily injections of 15 mg/kg, i.p.) and drug-naive rats during a test of cue-evoked incentive motivation for food-the Pavlovian-to-instrumental transfer task. We found that prior cocaine exposure augmented both reward seeking and DA release triggered by the presentation of a reward-paired cue. Furthermore, cue-evoked DA signaling positively correlated with cue-evoked food seeking and was found to be a statistical mediator of this behavioral effect of cocaine. Taken together, these findings provide support for the hypothesis that repeated cocaine exposure enhances cue-evoked incentive motivation through augmented phasic mesolimbic DA signaling. This work sheds new light on a fundamental neurobiological mechanism underlying motivated behavior and its role in the expression of compulsive reward seeking