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PubMed2001

Dorsal anterior cingulate cortex: a role in reward-based decision making.

Dorsal anterior cingulate cortex (dACC) is a brain region that subserves cognition and motor control, but the mechanisms of these functions remain unknown. Human neuroimaging and monkey electrophysiology studies have provided valuable insights, but it has been difficult to link the two literatures. Based on monkey single-unit recordings, we hypothesized that human dACC is comprised of a mixture of functionally distinct cells that variously anticipate and detect targets, indicate novelty, influence motor responses, encode reward values, and signal errors. As an initial test of this conceptualization, the current event-related functional MRI study used a reward-based decision-making task to isolate responses from a subpopulation of dACC cells sensitive to reward reduction. As predicted, seven of eight subjects showed significant (P < 10(-4)) dACC activation when contrasting reduced reward (REDrew) trials to fixation (FIX). Confirmatory group analyses then corroborated the predicted ordinal relationships of functional MRI activation expected during each trial type (REDrew > SWITCH > CONrew > or = FIX). The data support a role for dACC in reward-based decision making, and by linking the human and monkey literatures, provide initial support for the existence of heterogeneity within dACC. These findings should be of interest to those studying reward, cognition, emotion, motivation, and motor control.

Adult↗

PubMed2002

Within-subject comparison of real and hypothetical money rewards in delay discounting.

A within-subject design, using human participants, compared delay discounting functions for real and hypothetical money rewards. Both real and hypothetical rewards were studied across a range that included $10 to $250. For 5 of the 6 participants, no systematic difference in discount rate was observed in response to real and hypothetical choices, suggesting that hypothetical rewards may often serve as a valid proxy for real rewards in delay discounting research. By measuring discounting at an unprecedented range of real rewards, this study has also systematically replicated the robust finding in human delay discounting research that discount rates decrease with increasing magnitude of reward. A hyperbolic decay model described the data better than an exponential model.

Adult↗

PubMed1993

Live-social-video reward maintains joystick task performance in bonnet macaques.

A number of studies have now indicated that monkeys of several species will perform hundreds of food-rewarded joystick tasks on a daily basis. Our goal in this study was to identify the level of joystick task performance that could be maintained by 10 sec. of live, color video of a conspecific social group contingent upon the completion of a joystick task. The subjects were five individually housed bonnet macaques that were highly experienced on joystick tasks. Performance with social-video reward was compared to that maintained by a 190-mg banana-flavored pellet reward and to a nonreward condition. Comparable levels of task activity were maintained by both video and pellet reward, whereas task activity nearly ceased in the absence of reward. Four of the five monkeys increased their levels of task activity between the first and second weeks of social-video reward.

Animals↗

PubMed1997

Rate of temporal discounting decreases with amount of reward.

The present, subjective value of a delayed reward is a decreasing function of the duration of the delay. This phenomenon is termed temporal discounting. To determine whether the amount of the reward influences the rate of temporal discounting, we had subjects choose between immediate and delayed hypothetical rewards of different amounts ($100, $2,000, $25,000, and $100,000 delayed rewards). As predicted by psychological models of the choice process, hyperbolic functions described the decrease in the subjective value of the delayed reward as the time until its receipt was increased (R2s from .86 to .99). Moreover, hyperbolic functions consistently provided more accurate descriptions of the data than did exponential functions predicted by an economic model of discounted utility. Rate of discounting decreased in a negatively accelerated fashion as the amount of the delayed reward increased, leveling off by approximately $25,000. These findings are interpreted in the context of different psychological models of choice, and implications for procedures to enhance self-control are discussed.

Adolescent↗

PubMed2002

Interaction of CRH and energy balance in the modulation of brain stimulation reward.

The rewarding effect produced by electrical stimulation of some lateral hypothalamic sites is modulated by chronic food restriction and weight loss. The sensitivity of the rewarding effect to restriction predicts the modulation of brain stimulation reward (BSR) by the adiposity hormone, leptin. The present study examined the effect of corticotropin-releasing hormone (CRH) on the rewarding effect of stimulating restriction-sensitive and restriction-insensitive sites. Chronic food restriction reduced frequency thresholds for BSR in half of the subjects but had no effect in the others. CRH increased thresholds only in subjects in which the rewarding effect was insensitive to restriction. In contrast, frequency thresholds remained stable in nearly all rats with restriction-sensitive stimulation sites. These findings provide further evidence that sensitivity to food restriction is an important factor in determining the influence of hormones and neuropeptides on brain reward circuitry.

Animals↗

PubMed1991

Effect of current on the maximum possible reward.

Using a 2-lever choice paradigm with concurrent variable interval schedules of reward, it was found that when pulse frequency is increased, the preference-determining rewarding effect of 0.5-s trains of brief cathodal pulses delivered to the medial forebrain bundle of the rat saturates (stops increasing) at values ranging from 200 to 631 pulses/s (pps). Raising the current lowered the saturation frequency, which confirms earlier, more extensive findings showing that the rewarding effect of short trains saturates at pulse frequencies that vary from less than 100 pps to more than 800 pps, depending on the current. It was also found that the maximum possible reward--the magnitude of the reward at or beyond the saturation pulse frequency--increases with increasing current. Thus, increasing the current reduces the saturation frequency but increases the subjective magnitude of the maximum possible reward.

Animals↗

PubMed1997

5-HT2C (HTR2C) serotonin receptor gene polymorphism associated with the human personality trait of reward dependence: interaction with dopamine D4 receptor (D4DR) and dopamine D3 receptor (D3DR) polymorphisms.

We recently reported an association between the long repeat allele of the dopamine D4 exon III receptor polymorphism and a human personality dimension, novelty seeking, as measured by the tridimensional personality questionnaire (TPQ), a personality instrument designed by Cloninger to reflect heritable facets of human temperament. The D4 receptor polymorphism (D4DR) accounts for only a small percent of the variance for this trait, suggesting that additional genes influence both novelty seeking as well as the other temperaments that are inventoried by the Cloninger TPQ. In the current investigation, we examined, in the original cohort of 120 normal volunteers, two additional coding region polymorphisms, a glycine to serine substitution in the dopamine D3 receptor (D3DR) and a cysteine to serine substitution in the 5-HT2C serotonin receptor (HTR2C). Three-way analysis of variance (TPQ score grouped by D4DR, D3DR and 5-HT2C) demonstrated that reward dependence and persistence scores were significantly reduced by the presence of the less common 5-HT2Cser polymorphism. The effect of the serine substitution in this X-linked serotonin receptor polymorphism on reward dependence was also observed when male and female subject groups were separately analyzed. There was also a significant interaction between the two dopamine receptor polymorphisms and the serotonin polymorphism on reward dependence. In particular, the effect of the 5-HT2C polymorphism on reward dependence was markedly accentuated in individuals who had the long version of the D4DR exon III repeat polymorphism. When present in the same individual, the 5-HT2C and dopamine receptor polymorphisms account for 30% of the observed variance for persistence (RD2) and 13% of the variance for reward dependence scores (RD134). However, the number of subjects with both less common D4DR and 5-HT2C polymorphisms is small, underscoring the importance of verifying this interaction in a larger cohort.

Adult↗

PubMed2001

Alcohol abuse and dysfunctional eating in adolescent girls: the influence of individual differences in sensitivity to reward and punishment.

OBJECTIVE: An unusually high comorbidity of eating disorders and alcohol abuse has been found in clinical and community samples of young women. This paper proposes that individual differences in sensitivity to reward and punishment may influence the propensity of young women to engage in dysfunctional eating and drinking behaviour. METHOD: The Drive for Thinness scale, the Alcohol Use Disorders Identification Test and the BIS/BAS scales were administered to 232 high school girls. RESULTS: Heightened sensitivity to reward was the better predictor of alcohol misuse while heightened sensitivity to both reward and punishment was predictive of dysfunctional eating. When categorised by group, alcohol abusing, dysfunctional eating, and comorbid girls reported greater sensitivity to reward than non-disordered girls. Girls with dysfunctional eating with and without comorbid alcohol abuse reported greater sensitivity to punishment than alcohol abusing only girls. DISCUSSION: These findings suggest that girls who abuse alcohol and have dysfunctional eating may share a vulnerability to heightened sensitivity to reward, yet be differentiated by sensitivity to punishment.

Adolescent↗

PubMed1997

Posttraining intraamygdala infusions of oxotremorine and propranolol modulate storage of memory for reductions in reward magnitude.

These experiments examined the effects of posttraining intraamygdala administration of the muscarinic agonist, oxotremorine, and the beta-noradrenergic antagonist, propranolol, on memory for reduction in reward magnitude. Male Sprague-Dawley rats (175-200 g) implanted with bilateral intraamygdala cannulae were food deprived (maintained at 80% of body weight) and trained to run a straight alley (six trials/day) for either ten 45-mg food pellets (high reward) or one 45-mg food pellet (low reward) for 10 days. In Experiment One, the animals in the high-reward group were than shifted to a one-pellet reward and immediately given intraamygdala infusions (0.5 microliter/side) of either oxotremorine (10 ng) or phosphate buffer. Shifted training continued for 4 more days and no further injections were given. Shifted animals given the buffer solution displayed an increase in runway latencies but returned to preshift latencies by the fifth day of shifted training. In contrast, animals given oxotremorine exhibited increased latencies through the fifth day. In Experiment Two, rats were trained as in Experiment. One but immediately following the shift received intraamygdala infusions of oxotremorine (10 ng), propranolol (0.3 microgram), both, or phosphate buffer. Shifted vehicle-injected rats returned to preshift performance by the fifth day of shifted training. Shifted propranolol rats returned to preshift latencies by the third day of shifted training. In contrast, the shifted oxotremorine and the shifted oxotremorine/propranolol rats displayed longer latencies than unshifted controls through 5 days of shifted training. The findings indicate that the muscarinic cholinergic and beta-noradrenergic systems within the amygdala interact in regulating memory and support the view that noradrenergic influences are mediated through cholinergic activation.

Amygdala↗

PubMed1986

Anatomical disassociation of amphetamine's rewarding and aversive effects: an intracranial microinjection study.

Amphetamine has rewarding properties in some behavioral paradigms, such as self-administration and conditioned place preference (CPP), but an aversive component is also apparent when the drug is tested with the conditioned taste aversion (CTA) paradigm. The present study was an attempt to determine the neuroanatomical substrates of the drug's rewarding and aversive effects. Previous evidence suggested that amphetamine's stimulation of activity in dopaminergic synapses is critical for both effects. Amphetamine was therefore micro-injected bilaterally (10 micrograms/0.5 microliter per side) into six different dopaminergic sites, each in a different group of animals: the medial prefrontal cortex, nucleus accumbens, anteromedial caudate nucleus, lateroventral caudate nucleus, amygdala, and the region subjacent to the area postrema (AP region). The effects of these injections in both the taste and place conditioning paradigms were examined in separate experiments. Of the six sites, a significant CPP was observed only with accumbens injections and a significant CTA was observed only with AP region injections. It was concluded that the accumbens plays a primary role in mediating the rewarding effects of amphetamine and that the AP region plays a primary role in mediating the CTA. This constitutes an anatomical disassociation of amphetamine's rewarding and aversive effects. The differential associative bias of place-reward and taste-aversion learning apparent in the results is discussed.

Amygdala↗

PubMed1988

The threshold lowering effects of MDMA (ecstasy) on brain-stimulation reward.

3,4-Methylenedioxymethamphetamine (MDMA) is a psychoactive phenylisopropylamine which is structurally similar to both amphetamine-related sympathomimetics and the hallucinogen, mescaline. MDMA produces pleasurable effects which include euphoria, and recent reports continue to demonstrate its widespread recreational use. The aim of the present study was to assess the effects of racemic MDMA on the threshold for rewarding intracranial self-stimulation, an animal model used to assess a drug's abuse liability in man. Rewarding electrical stimulation was delivered via electrodes stereotaxically implanted in the medial forebrain bundle-lateral hypothalamic area of the rat brain. Thresholds were determined by means of a rate-independent psychophysical method. MDMA produced a dose-related lowering of the reward threshold in all four animals tested. Given that increased sensitivity for rewarding brain stimulation, measured as a lowering of the reward threshold, is an animal model of drug-induced euphoria these results suggest a similar mode of action for its reinforcing effects as other abused substances.

3,4-Methylenedioxyamphetamine↗

PubMed1975

Norepinephrine and serotonin: specificity of release with rewarding electrical stimulation of the brain.

Using a push-pull cannula method the amygdala of rats was perfused to examine the release of labeled norepinephrine (NE) and labeled serotonin (5-HT) during electrical stimulation of the brain (ESB) determined by prior behavioral testing to be rewarding or non-rewarding. Simple sensory stimulation was used during perfusion to examine further the degree of specificity of release of these amines. Highly rewarding ESB, but not the sensory stimulation, was accompanied by release of both NE and 5-HT. Varying current intensity had significant effects on the amount of these amines released. Furthermore, non-rewarding ESB was accompanied by inhibition of release of NE and 5-HT and a control substance, urea, was not significantly released during rewarding ESB. The results were discussed as implicating both noradrenergic and serotonergic mechanisms in the mediation of reinforcement.

Amygdala↗

PubMed1979

Interaction of alcohol and reward in an achievement situation.

Effects of psychological stress on acute alcohol intoxication following intake of 2 ml whisky/kg body weight were examined in 12 healthy subjects. Each subject performed a 45-min psychomotor task under four conditions, two of which increased achievement stress by promising the subject a monetary reward for rapid and accurate performance. The conditions were (a) task only, (b) task + reward, (c) task + alcohol, and (d) task + reward + alcohol. In condition (b) reward improved performance and heightened both physiological and subjective arousal, and in condition (c) alcohol impaired performance, lowered subjective arousal, and increased physiological arousal. In condition (d) the reward counteracted the depressant effects of alcohol on performance and mood, whereas an additive, arousing effect was obtained in all physiological variables, i.e., catecholamine and cortisol excretion and heart rate.

Achievement↗

PubMed1989

Repeated exposures intensify rather than diminish the rewarding effects of amphetamine, morphine, and cocaine.

It is commonly believed that repeated exposures diminish the pleasurable effects of drugs and hence that pleasure must have only a minor role in addiction. In six experiments with rats, repeated exposures to amphetamine, morphine, or cocaine were found to enhance the drug-induced rewarding effect as measured by conditioned place preference. Thus, sensitization to the rewarding effect, rather than tolerance, was obtained. Also, cross-sensitization was obtained; exposures to amphetamine enhanced the rewarding effect of morphine and vice versa; similarly, exposures to morphine enhanced the rewarding effect of cocaine. These findings support a new theory: drugs of abuse are addictive because repeated exposures sensitize the central reward mechanism so that drug taking produces a progressively greater reinforcing effect each time it occurs.

Amphetamine↗

PubMed1983

Effects of reward on delayed reaction time task performance of hyperactive children.

This experiment was designed to investigate the effects of continuous, partial, and noncontingent schedules of reward, as well as the withdrawal of rewards, on the performance of hyperactive and normal control children on a delayed reaction time task. Although noncontingent reward resulted in faster reaction times for control subjects, performance of hyperactives deteriorated under noncontingent reward and improved when it was withdrawn. Also, reaction times of controls during extinction remained superior to baseline, whereas performance of hyperactives returned to baseline level. It was suggested that these and other findings reviewed point to an unusual sensitivity to rewards in hyperactive children.

Attention Deficit Disorder with Hyperactivity↗

PubMed1975

The effects of reward and punishment on reaction times and autonomic activity in hyperactive and normal children.

The performance of hyperactive and control children was compared on a delayed reaction time task under three reinforcement conditions: reward, punishment, and reward plus punishment. Hyperactives had slower and more variable reaction times, suggesting an attentional deficit. Although each of the three reinforcement conditons was successful in improving reaction times for both subject groups, reward led to a significant increase in impulsive responses in the hyperactive children. Autonomic data revealed that reward also increased arousal to a greater extent than punishment or reward plus punishment. Although resting skin conductance was not different in the two groups of subjects, hyperactives produced fewer specific autonomic responses to signal stimuli.

Arousal↗

PubMed1992

Genetic differences in the rewarding and activating effects of morphine and ethanol.

The influence of genotype on the rewarding and locomotor activating effects of morphine and ethanol was examined in the place conditioning paradigm. Two inbred mouse strains (C57BL/6J and DBA/2J) were exposed to a differential conditioning procedure in which each mouse received four pairings of a distinctive floor stimulus with IP injection of morphine (0, 2.5, 5 or 10 mg/kg) or ethanol (0, 1, 2, 3 or 4 g/kg). A different floor stimulus was paired with saline. Conditioning trials lasted 30 min and each experiment concluded with a floor preference test in the absence of drug. In accord with previous studies, morphine evoked a dose-dependent increase in activity during conditioning that was greater in C57BL/6J mice than in DBA/2J mice. In contrast, ethanol produced a dose-dependent increase in activity that was greater in DBA/2J than in C57BL/6J mice. Both strains showed conditioned place preference with morphine, but only the DBA/2J strain showed conditioned place preference with ethanol. No conditioned place aversion was seen. With both drugs, stronger place preference conditioning was obtained in DBA/2J mice, supporting the general conclusion that sensitivity to drug reward is influenced by genotype. The fact that the same genotype is more sensitive to the rewarding effects of two different drugs supports theories postulating commonality in the biological mechanisms of drug reward. Although the outcome of the ethanol study supports predictions of the psychomotor stimulant theory of addiction concerning the relationship between drug-induced activation and reward, the outcome of the morphine study does not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1999

[Anhedonia--a general nosology surmounting correlate of a dysfunctional dopaminergic reward system?].

The dopaminergic reward system is activated by primary rewarding factors such as food, sexual activity and parental care. Its activation enhances the occurrence of behaviors which induced the stimulation of dopaminergic neurotransmission. Indications of a dysfunction of the dopaminergic reward system are found in major depression, schizophrenia, and addictive disorders. It has been hypothesized that dysfunction of the dopaminergic reward system is associated with anhedonia, the inability to experience pleasure. However, animal studies indicate that a reduction of central dopaminergic neurotransmission is associated with a decrease in incentive salience of reward-indicating stimuli and not with anhedonia per se. Sensitization of dopaminergic neurotransmission, on the other hand, seems to induce cue-dependent craving in addicted patients. In schizophrenia, phasic, stimulus-dependent dopamine release in the striatum may play a role in the abnormal attribution of salience to previously neutral stimuli.

Animals↗