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Reward without dopamine.

Dopamine (DA) is believed to play a fundamental role in reward processes. Virtually all drugs of abuse activate dopaminergic systems, as do "natural" rewards such as sexual interaction and food. Sweet-tasting solutions, for example, are a well characterized natural reward. In the present experiments, we used mice that cannot make DA (DD mice) to test the hypothesis that DA is necessary for reward. Sucrose preference, assessed with a computerized "lickometer," was used to determine whether DD mice respond preferentially for rewarding stimuli. DD mice preferentially chose sucrose over water, and also preferred the noncaloric sweetener saccharin. Furthermore, the rate of licking, bout size, and length were greater in DD mice drinking sweets than in controls. These data refute the necessity of DA for the reward processes manifested by sucrose preference. However, DD mice initiated licking less frequently than control mice and had fewer total licks. We suggest that DD mice have a deficit of goal-directed behavior that is not specific to reward processes. Lastly, juvenile DD mice demonstrate robust sucrose preference before experience with food in the presence of DA. Thus, DA is not required for mice to learn to consume sweet solutions preferentially. We conclude that DA is not required to find the sweet tastes of sucrose or saccharin rewarding.

Age Factors↗

Neuronal activity in monkey ventral striatum related to the expectation of reward.

Projections from cortical and subcortical limbic structures to the basal ganglia are predominantly directed to the ventral striatum. The present study investigated how the expectation of external events with behavioral significance is reflected in the activity of ventral striatal neurons. A total of 420 neurons were studied in macaque monkeys performing in a delayed go-no-go task. Lights of different colors instructed the animal to do an arm-reaching movement or refrain from moving, respectively, when a trigger light was illuminated a few seconds later. Task performance was reinforced by liquid reward in both situations. A total of 60 ventral striatal neurons showed sustained increases of activity before the occurrence of individual task events. In 43 of these neurons, activations specifically preceded the delivery of reward, independent of the movement or no-movement reaction. In a series of additional tests, these activations were time locked to the subsequent reward, disappeared within a few trials when reward was omitted, and were temporally unrelated to mouth movements. Changes in the appetitive value of the reward liquid modified the magnitude of activations, suggesting a possible relationship to the hedonic properties of the expected event. Activations also occurred when reward was delivered in a predictable manner outside of any behavioral task. These data suggest that neurons in the ventral striatum are activated during states of expectation of individual environmental events that are predictable to the subject through its past experience. The prevalence of activations related to the expectation of reward suggests that ventral striatal neurons have access to central representations of reward and thereby participate in the processing of information underlying the motivational control of goal-directed behavior.

Amygdala↗

Effects of multiple delayed rewards on delay discounting in an adjusting amount procedure.

It has been suggested that when the delivery of several rewards is separated in time, e.g. one reward immediately and a second reward a few moments later, the value of an alternative that includes these "bundled" rewards will be the sum of the hyperbolic discount functions of the individual rewards. The current study examined this hypothesis using an adjusting amount procedure. In this procedure, rats chose between a delayed food alternative and an immediate food alternative, where the amount of immediate food altered according to each rat's choices. The size of the immediate reward when rats were indifferent between the delayed and immediate alternatives indexed the value of the delayed alternative. Discount functions describing the relationship between the indifference points and the delay to food were created for conditions in which the delay alternative consisted of a single reward (150mul of sucrose solution) delayed by 0, 2, 4, 8, or 16s following the reinforced response. These functions were used to predict the indifference points in other conditions for which an additional 150mul of sucrose solution was delivered at 0, 4, 8, or 16s following the reinforced response. The model fit the data well. However, there were systematic deviations that suggested animals were sensitive to the context within which delays were presented, in addition to the delays themselves. That is, preference for the delayed alternative was lower than predicted when the delay to the additional reward was long (8 or 16s) and higher than the predicted values when it was short (0 or 4s).

Journal Article↗

Effects of sodium depletion on competition and summation between rewarding effects of salt and lateral hypothalamic stimulation in the rat.

The effect of sodium depletion on the value of lateral hypothalamic (LH) stimulation and on competition and summation between saline reward and LH reward was assessed. Sodium depletion did not alter curves relating the number of LH rewards earned per trial to the number of stimulation pulses per train, suggesting that negative sodium balance does not alter the reward value of the stimulation. In contrast, sodium depletion increased the ability of saline (0.9% NaCl) to compete with LH stimulation in a forced-choice preference test. Summation between the effects of the 2 rewards was also seen under sodium depletion. These findings imply that the rewarding effects of saline and LH stimulation are evaluated within a common system of measurement and that negative sodium balance modulates the value of the saline reward upstream from the point where the rewarding effects of saline and LH stimulation are combined.

Animals↗

Rewards for teaching excellence: practice in South African medical schools.

Excellence in teaching through recruitment of good teachers, rewarding good teaching and the creation of staff development programmes are priorities in the mission statement of most universities. Often, reality belies intention. At many universities serious attempts to ensure maximum teacher effectiveness, overt recognition of teaching excellence, and specific development funding are lacking. This study examines the extrinsic (i.e. financial) reward systems which operate at the eight medical schools attached to South African universities and reports on the current situation. Replies indicated that a reward system of some type operates within the university at seven South African universities which have faculties of medicine and embraces all faculties. One university rewards medical school teachers specifically but, at another, no reward system exists at all. The monetary value of rewards varies greatly. Significant criticism of all systems was the inability to meet their design aims. There was criticism of the criteria, such as they are and where they exist, used to identify teaching excellence and to reward recipients. All replies indicated support for an impartial and equitable system of reward for effectiveness and excellence in teaching.

Attitude↗

Probing brain reward system function in major depressive disorder: altered response to dextroamphetamine.

BACKGROUND: The state of the brain reward system in major depressive disorder was assessed with dextroamphetamine, which probes the release of dopamine within the mesocorticolimbic system, a major component of the brain reward system, and produces measurable behavioral changes, including rewarding effects (eg, euphoria). We hypothesized that depressed individuals would exhibit an altered response to dextroamphetamine due to an underlying brain reward system dysfunction reflected by anhedonic symptoms. METHODS: In a double-blind, placebo-controlled, randomized, parallel study, the behavioral and physiological effects of a single 30-mg dose of oral dextroamphetamine sulfate were measured. Forty patients with a diagnosis of DSM-IV major depressive disorder who were not taking antidepressant medications (22 assigned to dextroamphetamine and 18 to placebo) were compared with 36 control subjects (18 assigned to dextroamphetamine and 18 to placebo) using validated self-report drug effect measurement tools (eg, the Addiction Research Center Inventory), heart rate, and blood pressure. RESULTS: Multiple regression analysis showed that severity of depression as measured by the Hamilton Rating Scale for Depression correlated highly with the rewarding effects of dextroamphetamine in the depressed group (model R(2) = 0.63; interaction P =.04). A subsequent analysis categorizing the depressed group into patients with severe symptoms (Hamilton score >23) and those with moderate symptoms revealed a significant interaction between drug and depression (P =.02). Patients with severe symptoms reported rewarding effects 3.4-fold greater than controls. CONCLUSIONS: The results suggest the presence of a hypersensitive response is present in the brain reward system of depressed patients, which may reflect a hypofunctional state and may provide a novel pathophysiologic and therapeutic target for future studies.

Adult↗

Blockade of the reward-potentiating effects of nicotine on lateral hypothalamic brain stimulation by chlorisondamine.

Chlorisondamine, a quarternary nicotinic antagonist, was given in a dose that crosses the blood-brain barrier, is taken up and concentrated intracellularly by dopaminergic neurons, and induces long-term blockade of the locomotor stimulant and rewarding effects of nicotine. This treatment had no effect on the rewarding effects of lateral hypothalamic brain stimulation, failing to shift the function that relates reward strength to rate of responding (rate-frequency function). That the treatment regimen was sufficient to block nicotinic receptors in the reward system was confirmed by the fact that it completely blocked the ability of normally effective nicotine to potentiate the rewarding effects of stimulation (shift this function to the left). These data add evidence that the direct, endogenous cholinergic contribution to brain stimulation reward is muscarinic and fit with other evidence that the potentiation of brain stimulation reward by exogenous nicotine involves actions on nicotinic receptors native to dopaminergic neurons.

Animals↗

Partner's behavior, not reward distribution, determines success in an unequal cooperative task in capuchin monkeys.

It was recently demonstrated that capuchin monkeys notice and respond to distributional inequity, a trait that has been proposed to support the evolution of cooperation in the human species. However, it is unknown how capuchins react to inequitable rewards in an unrestricted cooperative paradigm in which they may freely choose both whether to participate and, within the bounds of their partner's behavior, which reward they will receive for their participation. We tested capuchin monkeys with such a design, using a cooperative barpull, which has been used with great success in the past. Contrary to our expectations, the equity of the reward distribution did not affect success or pulling behavior. However, the behavior of the partner in an unequal situation did affect overall success rates: pairs that had a tendency to alternate which individual received the higher-value food in unequal reward situations were more than twice as successful in obtaining rewards than pairs in which one individual dominated the higher-value food. This ability to equitably distribute rewards in inherently biased cooperative situations has profound implications for activities such as group hunts, in which multiple individuals work together for a single, monopolizable reward.

Animals↗

The effect of reward on compliance with breast self-examination.

Based on a behavioral analysis of compliance with breast self-examination (BSE), this study replicates a previously successful stimulus control intervention and tests the effectiveness of two types of reward for increasing compliance: external reward and self-reward. Patient volunteers (N = 153) were randomly assigned to experimental conditions and followed for 1 year, equally divided into experimental and postexperimental periods. Compliance was measured by the monthly return of BSE records, with self-reports used as a secondary measure. The results indicate that external reward was most effective; self-reward was used by only half the participants but was effective when used. In the postexperimental period, all rates of record return declined, especially in the external reward group. A cycle-by-cycle analysis indicates that the decline was gradual except for a sharp drop when the external reward was withdrawn. The results are discussed in terms of the acceptability of both interventions and contingencies.

Adult↗

Natural reward-related learning in rats with neonatal ventral hippocampal lesions and prior cocaine exposure.

RATIONALE: Psychostimulant injections in rats have been shown to alter future performance in natural reward conditioning. These effects may represent a persistent impact of drugs on neurocircuits that interface cognitive and motivational processes, which may be further altered in neuropsychiatric conditions that entail increased addiction vulnerability. OBJECTIVE: This study investigated whether a rat model of schizophrenia with cocaine addiction vulnerability shows altered natural reward conditioning with or without prior cocaine exposure. METHODS: Adult rats with SHAM or neonatal ventral hippocampal lesions were given cocaine (15 mg/kg per day for 5 days) or saline injections, followed 7 days later by natural reward-conditioned learning. Over ten daily sessions, water-restricted rats were assessed for durations of head entries into a magazine during random water presentations, a conditioning stimulus phase predictive of the water reward, and an "inappropriate" phase when conditioning stimuli were absent and reward presentation would be delayed. RESULTS: Over repeated sessions, lesioned and SHAM rats showed similar reductions in total magazine entry durations, with similar increases in the allocations of entry times during the water presentation. However, lesioned rats, especially those exposed to cocaine, demonstrated reduced allocations of magazine entry times during the conditioning stimulus phase, and increased allocations during the inappropriate phase. CONCLUSIONS: Intact natural reward motivation accompanied by deficient learning of complex contingencies to guide efficient reward approach may represent a form of impulsivity as an addiction vulnerability trait marker in an animal model of schizophrenia.

Animals↗

Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function.

RATIONALE: The transition from initial drug use to drug addiction has been proposed to result from an allostatic decrease in reward function driven by an overactivation of brain antireward processes. OBJECTIVES: How decreased reward function explains compulsive drug use is not entirely clear at present, and is still a subject for debate. METHODS: We present a quantitative model of cocaine self-administration that integrates pharmacokinetic, pharmacodynamic, and motivational factors to address this question. The model assumes that reward system responsivity is a homeostatically regulated process where the desired level of responsivity (called the reward set point) is initially different from the baseline level. The reduction or correction of this difference or error in reward function would drive cocaine self-administration. RESULTS: Theoretical data obtained by computer simulation fit the experimental data obtained in animals self-administering cocaine (i.e., the within-session pattern of self-injections, the shape and curvature of the dose-injection function, the nonlinear relationship between drug intake and regulated drug effects). Importantly, simulation of an allostatic decrease in reward system responsivity exacerbates the initial error that drives self-administration, thereby increasing both the intake of, and the motivation for, the drug. This allostatic change manifests as a vertical shift in the dose-injection function similar to that seen in animals with escalating cocaine self-administration. CONCLUSIONS: The present model provides a satisfactory explanation of escalated drug intake and suggests a novel negative reinforcement view of addiction based on an allostatic decrease in reward function.

Adaptation, Physiological↗

Role of muscles accumbens dopamine D1 and D2 receptors in instrumental and Pavlovian paradigms of conditioned reward.

RATIONALE: This study investigated the role of nucleus accumbens dopamine D1 and D2 receptors in two different paradigms of conditioned reward. OBJECTIVE: We addressed the question whether accumbal dopamine is important for the motor or for the motivational components of reward. METHODS: We compared the effects of intra-accumbal infusion of the dopamine D1 receptor antagonist SCH23390 (0.3, 1.0, 3.0 microg) and the D2 receptor antagonist sulpiride (0.3, 1.0, 3.0 microg) on conditioned lever pressing for food, with the effects on the inhibition of the startle response by a conditioned reward signal. RESULTS: Both the D1 and the D2 antagonist dose-dependently attenuated conditioned lever pressing for reward under a fixed-ratio of responding and increased the consumption of freely available lab chow. However, the preference for freely available pellets, and the attenuation of the startle response in the presence of a conditioned stimulus predicting reward were not impaired by blockade of accumbal dopamine receptors. CONCLUSIONS: Our data support the idea that dopamine in the nucleus accumbens is necessary for instrumental response selection in the context of reward rather than for the mere motor performance of behavior or for the evaluation of the hedonic properties of rewarding stimuli.

Animals↗

Spatially selective reward site responses in tonically active neurons of the nucleus accumbens in behaving rats.

To study how hippocampal output signals conveying spatial and other contextual information might be integrated in the nucleus accumbens, tonically active accumbens neurons were recorded in three unrestrained rats as they performed spatial orientation tasks on an elevated round rotatable platform with four identical reward boxes symmetrically placed around the edge. The partially water-deprived rats were required to shuttle either between the pair of reward boxes indicated by beacon cues (lights in the boxes) or between the pair of boxes occupying particular locations in relation to environmental landmark cues. In 43/82 neurons, behaviorally correlated phasic modulations in discharge activity occurred, primarily prior to or after water was provided at the reward boxes. Twenty-two had inhibitory modulation, 12 excitatory, and nine were mixed excitatory and inhibitory. Although tonically active neurons (TANs) have rarely been reported in the rodent, the inhibitory and mixed responses correspond to previously reports in the macaque accumbens of tonically active neurons with activity correlated with reward delivery and, following conditioning, to sensory stimuli associated with rewards. Eighteen of the 43 tonically active accumbens neurons showed spatial selectivity, i.e., behaviorally correlated increases or decreases in firing rate were of different magnitudes at the respective reward boxes. This is the first demonstration that the configuration of environmental sensory cues associated with reward sites are also an effective stimulus for these neurons and that different neurons are selective for different places. These results are consistent with a role for the nucleus accumbens in the initiation of goal-directed displacement behaviors.

Animals↗

Striatal dopamine release in the rat during a cued lever-press task for food reward and the development of changes over time measured using high-speed voltammetry.

Substantia nigra dopamine neuronal activity in the primate is thought to be related to the error in predicting reward delivery. Dopamine release in rat nucleus accumbens has been shown to increase in relation to drug/food-seeking behaviour. It is not known how the release of dopamine in the striatum corresponds to the many distinct steps of a rewarded, cued task (e.g. recognizing the cue, executing the behaviour, anticipating the reward, receiving the reward) and how dopamine release then changes over time as task performance improves. To investigate dopamine release during a rewarded, cued task and the development of changes in dopamine release over time, changes in extracellular striatal dopamine concentration during a rewarded, cued lever-press task were measured a few days every week for 5 months using high-speed in vivo voltammetry. Rats were trained to press a lever after a tone to obtain a food reward. The reaction time for the lever press decreased gradually as training continued. Changes in dopamine concentration were measured in the anterior striatum (ventral portion) during the task performance after an initial 6-day familiarization period, in which the animals learned that a lever press yielded food, and a 5-week period for surgery, recovery, and electrode preparation. During the task performance, dopamine concentration started to increase just after the cue, peaked near the time of the lever press, and returned to basal levels 1-2 s after the lever press. This pattern of changes in dopamine concentration was observed over the 5 months of testing, the peak dopamine concentration increasing steadily until peaking at week 7, at which time the task performance had not yet improved significantly from week 2. By week 13, task performance had significantly improved and peak dopamine concentration had begun to subside. Thus, the increase in dopamine concentration after the cue was highest while the task was not yet perfected and subsided toward the end of the learning process. It was concluded that striatal dopamine release during a cued lever-press task is relevant to the novelty of the conditions.

Animals↗

Changes in brain activation associated with reward processing in smokers and nonsmokers. A positron emission tomography study.

Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H2(15O)] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded.

Adult↗

Histone Arginine Methylation Regulates Neuropeptide Y Expression in the Basolateral Amygdala to Promote Reward-Seeking Behaviour.

The basolateral amygdala (BLA) serves in the evaluation of reward. However, the causal molecular substrates in the BLA necessary for reward seeking behaviour are largely unknown. Reward conditioning induces long-lasting changes in epienzymes in limbic areas, including the amygdala. The current study probed the role of histone arginine methylation as a novel epigenetic mechanism in neuropeptide Y (NPY) gene regulation in the BLA during reward and reinforcement. For reward conditioning, adult Wistar rats were trained to self-administer sucrose pellets in a nose-poke operant chamber. Reward conditioning increased protein arginine methyltransferase 4 (PRMT4) and NPY in the BLA. Moreover, after operant conditioning, histone arginine methylation (H3R17me2a) and PRMT4 occupancy at the NPY promoter were heightened. PRMT4 was predominantly colocalised in the nucleus of the NPY-expressing cells in the BLA. Intra-BLA administration of specific siRNA or inhibitor of PRMT4 after conditioning waned the nose-poke activity, which was further reinstated during the subsequent 5 days. These effects of PRMT4 repression were correlated with the NPY expression and H3R17me2a levels at the NPY promoter. Furthermore, NPY peptide administration after PRMT4 siRNA or inhibitor infusion in BLA restored the nose-poke activity. PRMT4 is known to interact with CREB-binding protein (CBP). Therefore, co-occupancy of PRMT4 and CBP resulted in heightened histone acetylation (H3K14ac) in the conditioned rats. The current study suggests a pivotal role of PRMT4-mediated histone arginine methylation in NPY gene expression in the amygdala necessary for the reward-seeking behaviour.

Animals↗

NMDA-induced lesions of the nucleus accumbens or the ventral pallidum increase the rewarding efficacy of food to deprived rats.

The role of the nucleus accumbens (NAC) and ventral pallidum (VP) in food reward modulation was investigated using Heyman's [24] curve fitting approach in food deprived rats. All rats were maintained at 80% normal body weight, and trained to lever press for food reinforcement. Each rat was tested daily with a series of four variable-interval (VI) reinforcement schedules (80, 40, 20, and 10 s) designed to approximate an exponential distribution, and randomly administered in ascending or descending order. The maximum response rate (Rmax) and the reinforcement rate required to maintain half-maximal responding (Re50) were recorded for each rat's daily test session. Following the establishment of baseline responding, the excitotoxin N-methyl-D-aspartic acid (NMDA) was bilaterally administered into the NAC (30 micrograms per side) or VP (20 micrograms per side) over a 10 min period. Both groups displayed substantial damage to the intended structure, with the lateral regions typically sustaining more damage than medial regions, and minor damage to surrounding areas. When tested at three weeks post-lesion, a suppression of motor activity was evident in all animals when compared to pre-lesion baseline. Moreover, in almost all rats, Re50 decreased, suggesting that the rewarding efficacy of food had increased. These data are surprising, given the extensive literature on the relationship between damage in the NAC and loss of reward efficacy. However, based on pharmacological and anatomical findings, both brain regions have been divided into several subregions. Behavioral studies suggest that these subregions may differentially regulate reward and motor functions. The results from the present study suggest that (1) both the NAC and VP are involved in the modulation of food reward, (2) that lateral subregions in each structure may function to dampen food reward efficacy, and (3) that medial subregions may enhance food reward.

Animal Feed↗

Situational moderators of leader reward and punishment behaviors: fact or fiction?

One assumption shared by many contemporary models of leadership is that situational variables moderate the relationships between leader behaviors and subordinate responses. Recently, however, R. J. House and J. L. Baetz (1979 in B. Staw & L. Cummings, Eds., Research in Organizational Behavior (Vol. 1), Greenwich, Connecticut, JAI Press) have suggested that the effects of some leader traits and behaviors may be relatively invariant; that is, have the same effects in a variety of situations. One possible class of leader behaviors which may have relatively consistent effects across situations are those known as leader reward and punishment behaviors. The first goal of the research reported here was to increase our understanding of the relationships between leader contingent and noncontingent reward and punishment behaviors and subordinate responses. Contingent reward behavior was found to have the most pronounced relationships with subordinate performance and satisfaction, followed by noncontingent punishment behavior. Neither leader noncontingent reward nor contingent punishment behavior were found to be related to either subordinate performance or satisfaction, with the exception that noncontingent reward behavior was negatively related to subordinates' satisfaction with work. The second goal of the research was to examine the effects of a variety of potential moderators on the relationships between leader reward and punishment behaviors and subordinate responses. The results of this study suggest that the relationships between leader reward and punishment behaviors and subordinates' performance are relatively free of moderating effects.

Factor Analysis, Statistical↗