Differential effects of acute and prolonged morphine withdrawal on motivational and goal-directed control over reward-seeking behaviour.

Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence.

Differential effects of acute and prolonged morphine withdrawal on motivational and goal-directed control over reward-seeking behavior.

Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational, and cognitive processes involved in regulating the pursuit and consumption of natural food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence.

Long-term effects of THC exposure on reward learning and motivated behavior in adolescent and adult male rats.

Rationale: The endocannabinoid system makes critical contributions to reward processing, motivation, and behavioral control. Repeated exposure to THC or other cannabinoid drugs can cause persistent adaptions in the endocannabinoid system and associated neural circuitry. It remains unclear how such treatments affect the way rewards are processed and pursued.

Flexible control of Pavlovian-instrumental transfer based on expected reward value.

The Pavlovian-instrumental transfer (PIT) paradigm is widely used to assay the motivational influence of reward-predictive cues, reflected by their ability to invigorate instrumental behavior. Leading theories assume that a cue's motivational properties are tied to predicted reward value. We outline an alternative view that recognizes that reward-predictive cues may suppress rather than motivate instrumental behavior under certain conditions, an effect termed positive conditioned suppression.

Dorsomedial prefrontal cortex activation disrupts Pavlovian incentive motivation.

The dorsomedial prefrontal cortex (dmPFC) is known to make important contributions to flexible, reward-motivated behavior. However, it remains unclear if the dmPFC is involved in regulating the expression of Pavlovian incentive motivation, the process through which reward-paired cues promote instrumental reward-seeking behavior, which is modeled in rats using the Pavlovian-instrumental transfer (PIT) task. The current study examined this question using a bidirectional chemogenetic strategy in which inhibitory (hM4Di) or excitatory (hM3Dq) designer G-protein coupled receptors were virally expressed in dmPFC neurons, allowing us to later stimulate or inhibit this region by administering CNO prior to PIT testing.

Reward-predictive cues elicit excessive reward seeking in adolescent rats.

Impulsive behavior during adolescence may stem from developmental imbalances between motivational and cognitive-control systems, producing greater urges to pursue reward and weakened capacities to inhibit such actions. Here, we developed a Pavlovian-instrumental transfer (PIT) protocol to assay rats' ability to suppress cue-motivated reward seeking based on changes in reward expectancy. Traditionally, PIT studies focus on how reward-predictive cues motivate instrumental reward-seeking behavior (lever pressing).

Mesolimbic dopamine projections mediate cue-motivated reward seeking but not reward retrieval in rats.

Efficient foraging requires an ability to coordinate discrete reward-seeking and reward-retrieval behaviors. We used pathway-specific chemogenetic inhibition to investigate how rats' mesolimbic and mesocortical dopamine circuits contribute to the expression and modulation of reward seeking and retrieval. Inhibiting ventral tegmental area dopamine neurons disrupted the tendency for reward-paired cues to motivate reward seeking, but spared their ability to increase attempts to retrieve reward.

Nucleus Accumbens Cholinergic Interneurons Oppose Cue-Motivated Behavior.

Background: Environmental reward-predictive stimuli provide a major source of motivation for adaptive reward pursuit behavior. This cue-motivated behavior is known to be mediated by the nucleus accumbens (NAc) core. The cholinergic interneurons in the NAc are tonically active and densely arborized and thus well suited to modulate NAc function.

The push and pull of dopamine in cue-reward learning.

A recent study by Saunders, Richard, Margolis, and Janak (2018) shows that there is a great deal left to learn about what different mesotelencephalic dopamine circuits contribute to learning about the motivational significance of reward-related cues. Their findings suggest that nigrostriatal and mesolimbic dopamine pathways support distinct reinforcement processes that independently push and pull animals toward their goals.

Junk Food Exposure Disrupts Selection of Food-Seeking Actions in Rats.

There is growing evidence that repeated consumption of highly palatable, nutritionally poor "junk food" diets can produce deficits in cognition and behavioral control. We explored whether long-term junk-food diet exposure disrupts rats' ability to make adaptive choices about which foods to pursue based on (1) expected reward value (outcome devaluation test) and (2) cue-evoked reward expectations (Pavlovian-to-instrumental test). Rats were initially food restricted and trained on two distinct response-outcome contingencies (e.

Repeated cocaine exposure dysregulates cognitive control over cue-evoked reward-seeking behavior during Pavlovian-to-instrumental transfer.

Drug-paired cues acquire powerful motivational properties, but only lead to active drug-seeking behavior if they are potent enough to overwhelm the cognitive control processes that serve to suppress such urges. Studies using the Pavlovian-to-instrumental transfer (PIT) task have shown that rats pretreated with cocaine or amphetamine exhibit heightened levels of cue-motivated food-seeking behavior, suggesting that exposure to these drugs sensitizes the incentive motivational system. However, the PIT testing protocol can also create conflict between two competing behavioral responses to the reward-paired cue: active reward seeking (e.

Contributions of Pavlovian incentive motivation to cue-potentiated feeding.

Cues signaling the availability of palatable food acquire the ability to potentiate food seeking and consumption. The current study employed a combination of behavioral, pharmacological, and analytical techniques to probe the role of Pavlovian incentive motivation in cue-potentiated feeding. We show that a cue paired with sucrose solution (CS+) can transfer its control over feeding to stimulate sucrose consumption at a new receptacle, and that this effect depends on activation of D1 dopamine receptors, which is known to modulate other forms of cue-motivated behavior but not taste palatability.

Beta-arrestin 1 regulation of reward-motivated behaviors and glutamatergic function.

The two highly homologous non-visual arrestins, beta-arrestin 1 and 2, are ubiquitously expressed in the central nervous system, yet knowledge of their disparate roles is limited. While beta-arrestin 2 (βarr2) has been implicated in several aspects of reward-related learning and behavior, very little is known about the behavioral function of beta-arrestin 1 (βarr1). Using mice lacking βarr1, we focused on the role of this scaffolding and signal transduction protein in reward-motivated behaviors and in striatal glutamatergic function.

Sex-specific enhancement of palatability-driven feeding in adolescent rats.

It has been hypothesized that brain development during adolescence perturbs reward processing in a way that may ultimately contribute to the risky decision making associated with this stage of life, particularly in young males. To investigate potential reward dysfunction during adolescence, Experiment 1 examined palatable fluid intake in rats as a function of age and sex. During a series of twice-weekly test sessions, non-food-deprived rats were given the opportunity to voluntarily consume a highly palatable sweetened condensed milk (SCM) solution.

Modulation of cue-triggered reward seeking by cholinergic signaling in the dorsomedial striatum.

The dorsomedial striatum (DMS) has been strongly implicated in flexible, outcome-based decision making, including the outcome-specific Pavlovian-to-instrumental transfer effect (PIT), which measures the tendency for a reward-predictive cue to preferentially motivate actions that have been associated with the predicted reward over actions associated with different rewards. Although the neurochemical underpinnings of this effect are not well understood, there is growing evidence that striatal acetylcholine signaling may play an important role. This study investigated this hypothesis by assessing the effects of intra-DMS infusions of the nicotinic antagonist mecamylamine or the muscarinic antagonist scopolamine on expression of specific PIT in rats.

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation.

Environmental reward-predictive cues can motivate reward-seeking behaviors. Although this influence is normally adaptive, it can become maladaptive in disordered states, such as addiction. Dopamine release in the nucleus accumbens core (NAc) is known to mediate the motivational impact of reward-predictive cues, but little is known about how other neuromodulatory systems contribute to cue-motivated behavior.

A Closer Look at the Effects of Repeated Cocaine Exposure on Adaptive Decision-Making under Conditions That Promote Goal-Directed Control.

It has been proposed that compulsive drug seeking reflects an underlying dysregulation in adaptive behavior that favors habitual (automatic and inflexible) over goal-directed (deliberative and highly flexible) action selection. Rodent studies have established that repeated exposure to cocaine or amphetamine facilitates the development of habits, producing behavior that becomes unusually insensitive to a reduction in the value of its outcome. The current study more directly investigated the effects of cocaine pre-exposure on goal-directed learning and action selection using an approach that discourages habitual performance.

Involvement of Endogenous Enkephalins and β-Endorphin in Feeding and Diet-Induced Obesity.

Studies implicate opioid transmission in hedonic and metabolic control of feeding, although roles for specific endogenous opioid peptides have barely been addressed. Here, we studied palatable liquid consumption in proenkephalin knockout (PENK KO) and β-endorphin-deficient (BEND KO) mice, and how the body weight of these mice changed during consumption of an energy-dense highly palatable 'cafeteria diet'. When given access to sucrose solution, PENK KOs exhibited fewer bouts of licking than wild types, even though the length of bouts was similar to that of wild types, a pattern that suggests diminished food motivation.

Inflated reward value in early opiate withdrawal.

Through incentive learning, the emotional experience of a reward in a relevant need state (e.g. hunger for food) sets the incentive value that guides the performance of actions that earn that reward when the need state is encountered again.

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.

Targeted expression of μ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward.

μ-opioid receptors (MORs) are necessary for the analgesic and addictive effects of opioids such as morphine, but the MOR-expressing neuronal populations that mediate the distinct opiate effects remain elusive. Here we devised a new conditional bacterial artificial chromosome rescue strategy to show, in mice, that targeted MOR expression in a subpopulation of striatal direct-pathway neurons enriched in the striosome and nucleus accumbens, in an otherwise MOR-null background, restores opiate reward and opiate-induced striatal dopamine release and partially restores motivation to self administer an opiate. However, these mice lack opiate analgesia or withdrawal.

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.