Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “REWARD”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed2001

Reward mechanisms in the brain and their role in dependence: evidence from neurophysiological and neuroimaging studies.

This article reviews neuronal activity related to reward processing in primate and human brains. In the primate brain, neurophysiological methods provide a differentiated view of reward processing in a limited number of brain structures. Dopamine neurons respond to unpredictable rewards and produce a global reinforcement signal. Some neurons in the striatum also react to the expectation and detection of reward. Other striatal neurons show reward-related activities related to the preparation, initiation and execution of movement. Orbitofrontal neurons discriminate among different rewards and code reward preferences. In the human brain, regions belonging to a meso-striatal and meso-corticolimbic loop respond to reinforcement stimuli in control subjects. These observations corroborate results obtained in primates. Additionally, reward induces activation in regions specific to task performance. Our results also show a similar pattern of reward-related activation in nicotine and opiate addicts. Thus, in contrast to healthy subjects, typical reward-related regions respond in addicts to monetary reward but not to nonmonetary reinforcement. Reduced activation in performance-related regions is also observed in both groups of dependent subjects. The results of animal and human studies suggest that dopamine and dopamine-related regions are associated with the integration of motivational information and movement execution. Dopamine-related pathological disorders can be associated with movement disorders, such as Parkinson's disease or with false motivational attributions such as drug dependence.

Animals↗
PubMed1999

Excessive discounting of delayed rewards in substance abusers with gambling problems.

This study evaluated delay discounting functions of substance abusing problem gamblers, substance abusing non-problem gamblers, and non-problem gambling/non-substance abusing controls. Subjects chose between hypothetical monetary amounts available after various delays or immediately. In one condition, a USUS$1000 reward was delayed at intervals ranging from 6 h to 25 years. At each delay interval, the immediately available rewards varied from USUS$1 to USUS$999 until choices reflected indifference between the smaller immediate and larger delayed rewards. In a second condition, the delayed reward was USUS$100, and immediate rewards varied from USUS$0.10 to USUS$99.90. In all three groups, hyperbolic discounting functions provided a good fit of the data, and the smaller reward was discounted at a higher rate than the larger reward. Substance abusers discounted delayed rewards at significantly higher rates than non-substance abusing controls, and problem gambling substance abusers discounted delayed rewards at higher rates than their non-problem gambling substance abusing counterparts. Discounting rates were not associated with types or recency of drug use. These results provide further evidence of more rapid discounting of delayed rewards in substance abusers, and especially among substance abusers with a comorbid gambling problem. Rapid discounting of delayed rewards may be a feature central to impulse control and addictive disorders.

Adult↗
PubMed1996

Addictive drugs and brain stimulation reward.

Direct electrical or chemical stimulation of specific brain regions can establish response habits similar to those established by natural rewards such as food or sexual contact. Cocaine, mu and delta opiates, nicotine, phencyclidine, and cannabis each have actions that summate with rewarding electrical stimulation of the medial forebrain bundle (MFB). The reward-potentiating effects of amphetamine and opiates are associated with central sites of action where these drugs also have their direct rewarding effects, suggesting common mechanisms for drug reward per se and for drug potentiation of brain stimulation reward. The central sites at which these and perhaps other drugs of abuse potentiate brain stimulation reward and are rewarding in their own right are consistent with the hypothesis that the laboratory reward of brain stimulation and the pharmacological rewards of addictive drugs are habit forming because they act in the brain circuits that subserve more natural and biologically significant rewards.

Animals↗
PubMed2006

Basal ganglia orient eyes to reward.

Expectation of reward motivates our behaviors and influences our decisions. Indeed, neuronal activity in many brain areas is modulated by expected reward. However, it is still unclear where and how the reward-dependent modulation of neuronal activity occurs and how the reward-modulated signal is transformed into motor outputs. Recent studies suggest an important role of the basal ganglia. Sensorimotor/cognitive activities of neurons in the basal ganglia are strongly modulated by expected reward. Through their abundant outputs to the brain stem motor areas and the thalamocortical circuits, the basal ganglia appear capable of producing body movements based on expected reward. A good behavioral measure to test this hypothesis is saccadic eye movement because its brain stem mechanism has been extensively studied. Studies from our laboratory suggest that the basal ganglia play a key role in guiding the gaze to the location where reward is available. Neurons in the caudate nucleus and the substantia nigra pars reticulata are extremely sensitive to the positional difference in expected reward, which leads to a bias in excitability between the superior colliculi such that the saccade to the to-be-rewarded position occurs more quickly. It is suggested that the reward modulation occurs in the caudate where cortical inputs carrying spatial signals and dopaminergic inputs carrying reward-related signals are integrated. These data support a specific form of reinforcement learning theories, but also suggest further refinement of the theory.

Animals↗
PubMed2005

Neuronal activity representing temporal prediction of reward in the primate prefrontal cortex.

Temporal prediction of future events, especially regarding reward delivery, is critical for controlling/learning purposeful behavior. The dorsolateral prefrontal cortex (DLPFC) has been considered to be involved in behavioral control based on prospective coding for future events, including reward. Thus this area is likely to have a neuronal mechanism responsible for temporal prediction of forthcoming reward. To address this hypothesis, we recorded the neuronal activity from the DLPFC of macaque monkeys while they performed an oculomotor delayed-response task under two conditions regarding the time of reward delivery. In this task, when the subjects made a correct response, the reward was delivered after a reward-delay period of 0.5 or 2 s. At the behavioral level, the onset latency for saccades was significantly faster in the shorter reward-delay trials (0.5 s) than in longer reward-delay trials (2 s), indicating that our subjects actually predicted the time of reward delivery. At the neuronal level, we found that many DLPFC neurons showed differential activity depending on the predicted time of reward delivery during the cue and/or delay periods. These results suggest that a fraction of neurons in the DLPFC represent the temporal prediction of reward and probably a variety of other future events.

Action Potentials↗
PubMed2001

Influence of expectation of different rewards on behavior-related neuronal activity in the striatum.

This study investigated how different expected rewards influence behavior-related neuronal activity in the anterior striatum. In a spatial delayed-response task, monkeys reached for a left or right target and obtained a small quantity of one of two juices (apple, grenadine, orange, lemon, black currant, or raspberry). In each trial, an initial instruction picture indicated the behavioral target and predicted the reward. Nonmovement trials served as controls for movement relationships. Consistent preferences in special reward choice trials and differences in anticipatory licks, performance errors, and reaction times indicated that animals differentially expected the rewards predicted by the instructions. About 600 of >2,500 neurons in anterior parts of caudate nucleus, putamen, and ventral striatum showed five forms of task-related activations, comprising responses to instructions, spatial or nonspatial activations during the preparation or execution of the movement, and activations preceding or following the rewards. About one-third of the neurons showed different levels of task-related activity depending on which liquid reward was predicted at trial end. Activations were either higher or lower for rewards that were preferred by the animals as compared with nonpreferred rewards. These data suggest that the expectation of an upcoming liquid reward may influence a fraction of task-related neurons in the anterior striatum. Apparently the information about the expected reward is incorporated into the neuronal activity related to the behavioral reaction leading to the reward. The results of this study are in general agreement with an account of goal-directed behavior according to which the outcome should be represented already at the time at which the behavior toward the outcome is performed.

Animals↗
PubMed2006

Comparison of reward modulation in the frontal eye field and caudate of the macaque.

The frontal eye field (FEF) influences saccade generation via direct projections to the superior colliculus and an indirect pathway through the basal ganglia. To test whether different reward information is represented in the FEF and the basal ganglia, we recorded from the FEF and the caudate nucleus in monkeys performing an asymmetrically rewarded memory-guided saccade task. A peripheral cue at one of two opposing positions was flashed briefly to indicate the saccade target. In a given block, one position was associated with big reward and the other with small reward. Big-reward position was alternated between blocks. In this task, the FEF and caudate displayed similar prevalence of neuronal activity before cue onset that was larger in blocks with specific big reward-cue position associations. They also exhibit comparable reward modulation of visual responses that were spatially selective. In contrast, visual responses that were specific to expected reward size, instead of spatial locations, were commonly observed in caudate but rarely seen in the FEF. Thus, both the FEF and basal ganglia may contribute to reward bias in saccade generation, with the FEF providing spatially relevant reward information and the basal ganglia providing additional reward-specific information.

Action Potentials↗
PubMed2006

Rule learning and reward contingency are associated with dissociable patterns of dopamine activation in the rat prefrontal cortex, nucleus accumbens, and dorsal striatum.

The midbrain dopamine system has been ascribed roles in reward expectancy, error detection, prediction, and memory. However, these theories typically do not differentiate between dopamine response and action in different forebrain terminal fields. We measured dopamine release in the prefrontal cortex (PFC), nucleus accumbens (NAc), and dorsal striatum (DS) of rats exposed to the same maze apparatus under three behavioral conditions: a set-shift task in which reward depended on discrimination learning and extradimensional set-shifting, a yoked condition in which reward was intermittent and not under the control of the subject, and a "reward-retrieval" variant in which reward was certain on every trial. We found dissociable patterns of dopamine release associated with learning, uncertainty, and reward. Dopamine increased in all three regions when reward was contingent on rule learning and shifting or was uncertain. These increases were sustained after behavior. There was a significant correlation between the magnitude of increase in PFC dopamine and the rapidity with which rats shifted between discrimination rules. In the yoke condition, in which the receipt of reward was always uncertain, the opposite relationship between dopamine levels and likelihood of reward was observed. Predictable, noncontingent reward was associated with increased dopamine levels in the NAc and DS. In contrast, PFC dopamine did not increase significantly above baseline levels. Thus, the dopaminergic projections to the PFC and nucleus accumbens were selectively, yet differentially, activated in situations of uncertainty and cognitive demand, whereas the dopaminergic projection to the DS responded independently of task differences in learning and reward.

Animals↗
PubMed2006

Reward association affects neuronal responses to visual stimuli in macaque te and perirhinal cortices.

To study the roles of the perirhinal cortex (PRh) and temporal cortex (area TE) in stimulus-reward associations, we recorded spike activities of cells from PRh and TE in two monkeys performing a visually cued go/no-go task. Each visual cue indicated the required motor action as well as the availability of reward after correct completion of the trial. Eighty object images were divided into four groups, each of which was assigned to one of four motor-reward conditions. The monkeys either had to release a lever (go response) or keep pressing it (no-go response), depending on the cue. Each of the go and no-go trials could be either a rewarded or unrewarded trial. A liquid reward was provided after correct responses in rewarded trials, whereas correct responses were acknowledged only by audiovisual feedback in unrewarded trials. Several measures of the monkeys' behavior indicated that the monkeys correctly anticipated the reward availability in each trial. The dependence of neuronal activity on the reward condition was examined by comparing mean discharges to each of the 40 rewarded stimuli with those to each of the 40 unrewarded stimuli. Many cells in both areas showed significant reward dependence in their responses to the visual cues, and this was not likely attributable to differences in behavior across conditions because the variations in neuronal activity were not correlated with trial-by-trial variations in latency of go responses or anticipatory sucking strength. These results suggest the involvement of PRh and TE in associating visual stimuli with reward outcomes.

Action Potentials↗
PubMed2004

Discounting of delayed food rewards in pigeons and rats: is there a magnitude effect?

Temporal discounting refers to the decrease in the present, subjective value of a reward as the time to its receipt increases. Results from humans have shown that a hyperbola-like function describes the form of the discounting function when choices involve hypothetical monetary rewards. In addition, magnitude effects have been reported in which smaller reward amounts are discounted more steeply than larger amounts. The present research examines the cross-species generality of these findings using real rewards, namely food pellets, with both pigeons and rats. As with humans, an adjusting amount procedure was used to estimate the amount of immediate reward judged equal in value to a delayed reward. Different amounts of delayed food rewards (ranging from 5 to 32 pellets in pigeons and from 5 to 20 pellets in rats) were studied at delays varying from 1 s to 32 s. A simple hyperbola, similar to the hyperbola-like mathematical function that describes the discounting of hypothetical monetary rewards in humans, described the discounting of food rewards in both pigeons and rats. These results extend the generality of the mathematical model of discounting. Rates of discounting delayed food rewards were higher for pigeons than for rats. Unlike humans, however, neither pigeons nor rats showed a reliable magnitude effect: Rate of discounting did not vary systematically as a function of the amount of the delayed reward.

Animals↗
PubMed2001

Sensitivity to reward delay in children with attention deficit hyperactivity disorder (ADHD).

The present study compared the sensitivity to pre- and post-reward delays of children with and without DSM-IV combined type ADHD. Thirty-six children with DSM-IV combined type ADHD and 36 controls completed a signal-detection task. Correct identification of one stimulus produced an immediate reward and then a 3.5 s delay before the next trial (immediate reward). Correct identification of the other stimulus was associated with a 3.5 s delay before reward was delivered (delayed reward). Group differences emerged in response bias toward the immediately rewarded alternative. Children in the ADHD group showed a greater bias toward immediate reward than the controls. Children in the control group showed different patterns of response bias and discriminability following immediate and delayed rewards. For these children discriminability was lower and response bias was greater on trials following delayed reward. Both groups responded more slowly on trials following delayed reward. These findings support the hypothesis that children with ADHD are unusually sensitive to pre-reward delays.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Role of tonically active neurons in primate caudate in reward-oriented saccadic eye movement.

Recent studies have suggested that the basal ganglia are essential for reward-oriented behavior. A popular proposal is that the interaction between sensorimotor and reward-related signals occurs in the striatal projection neurons. However, the role of interneurons remains unclear. Using the one-direction-rewarded version of the memory-guided saccade task (1DR), we examined the activity of tonically active neurons (TANs), presumed cholinergic interneurons, in the caudate. Many TANs (73/155, 47.1%) responded, usually with a pause, to a visual cue that indicated both the saccade goal and the presence or absence of reward. For most TANs (44/73, 60.3%), the response was spatially selective (contralateral dominant), but was not modulated by the reward significance. TANs are thus distinct from caudate projection neurons, which have responses to the cue that are both spatially selective and reward contingent, and from midbrain dopamine neurons, which have cue responses that are spatially nonselective and reward contingent. TANs were nonetheless sensitive to the reward schedule: in the all-directions-rewarded version (ADR) compared with 1DR, the cue responses of TANs were smaller, less frequent, and less spatially selective. In 1DR, it would first be detected that reward is not given regularly, and this process would then promote discrimination of individual stimuli in relation to reward. We propose that TANs would contribute to the detection of the context that requires discrimination, whereas dopamine neurons would contribute to the stimulus discrimination. These features of TANs might be explained by their cytoarchitecture, namely, as large aspiny neurons.

Action Potentials↗
PubMed1993

Drugs of abuse: biochemical surrogates of specific aspects of natural reward?

In this paper it is argued that drugs of abuse act on specific neurotransmitter pathways and by this mechanism elicit neurochemical changes that mimic some aspects of the overall pattern of the neurochemical effects of natural rewarding stimuli. Thus, drugs of abuse are biochemically homologous to specific aspects of natural rewarding stimuli. The behavioral similarity between drugs of abuse and natural stimuli, including that of being rewarding, results from their common property of activating neurochemically specific pathways. Natural stimuli accomplish this result indirectly through their sensory properties and incentive learning while drugs stimulate by a direct central action the critical reward pathways. Many drugs of abuse mimic the incentive properties of natural stimuli and their ability to stimulate mesolimbic dopamine pathways (Fig. 1). Both natural rewards and drugs of abuse, including amphetamine, cocaine and other psychostimulants, preferentially stimulate dopamine transmission in the mesolimbic nucleus accumbens compared with the dorsal caudate, an area related to the extrapyramidal motor system. Although many drugs of abuse mimic the incentive aspect of natural reward, this is probably not an absolute prerequisite for conferring to a drug some abuse liability. It might be predicted that certain drugs might be abused as a result of their action at sites located beyond dopamine or by mimicking other aspects of naturally rewarding stimuli such as the 'functional' (or trophotropic). This might be the case with opiates (which also mimic the 'incentive' aspect) and of benzodiazepines, as a result of activation of the central opioid reward system and of the central gamma-aminobutyric acid (GABA)-benzodiazepine system respectively. The hypothesis appears to have heuristic value as it predicts that biochemical mechanisms important for the rewarding properties of drugs of abuse are expected to play a role also in natural reward. One test of this hypothesis is offered by the observation that the 5-hydroxytryptamine (5-HT) system, through 5-HT3 receptors, and the central opioid system, through delta-opioid receptors, can contribute to the mechanism of the dopamine-activating properties of certain drugs of abuse. On this basis it would be predicted that drugs acting on 5-HT3 and on delta-opioid receptors would interfere with or mimic certain aspects of natural rewarding stimuli.

Animals↗
PubMed2001

Nicotine potentiation of brain stimulation reward reversed by DH beta E and SCH 23390, but not by eticlopride, LY 314582 or MPEP in rats.

RATIONALE: Systemic nicotine administration increases dopamine and glutamate levels in reward-related brain areas. Nicotine-induced increases of dopamine in the nucleus accumbens are in part mediated by glutamatergic projections to the ventral tegmental area dopamine neurons. OBJECTIVES: To assess the effects of actions at acetylcholine, dopamine, presynaptic (mGluR(2/3)) and postsynaptic (mGluR(5)) metabotropic glutamate receptors (mGluRs) on the potentiation of brain stimulation reward induced by systemically administered nicotine (0.125-0.5 mg/kg; free base) in rats. METHODS: A discrete-trial current-threshold s stimulation reward procedure (electrodes placed in the posterior lateral hypothalamus) was used to assess the effects of DH beta E (0.5-5 mg/kg), an acetylcholine nicotinic receptor antagonist, SCH 23390 (1.25-5 microg/kg), a dopamine D(1) receptor antagonist, eticlopride (2.5-20 microg/kg), a dopamine D(2) receptor antagonist, LY 314582 (1-20 mg/kg), an mGluR(2/3) agonist, and MPEP (1-9 mg/kg), an mGluR(5) antagonist, on the reward potentiating effects of nicotine (0.25 mg/kg). RESULTS: DH beta E had no effect on reward thresholds when administered alone, but dose-dependently reversed the nicotine-induced potentiation of brain stimulation reward. SCH 23390 (5 microg/kg) elevated thresholds when administered alone, and reversed the nicotine-induced potentiation of brain stimulation reward even at a dose (2.5 microg/kg) that had no effect on reward thresholds. Eticlopride (10-20 microg/kg), LY 314582 (10-20 mg/kg) and MPEP (9 mg/kg) elevated thresholds when administered alone but had no effect on the nicotine-induced potentiation of brain stimulation reward. CONCLUSIONS: These results indicate that nicotinic and dopamine D(1) receptors are involved in the nicotine-induced potentiation of brain stimulation reward, while actions at dopamine D(2), mGlu(2/3) and mGlu(5) receptors did not modulate this effect of nicotine.

Animals↗
PubMed2002

Cocaine and SKF-82958 potentiate brain stimulation reward in Swiss-Webster mice.

RATIONALE: The dopamine D(1)-like receptor agonist SKF-82958 reportedly blocks reinstatement of cocaine-seeking behavior in rats and non-human primates. It is not known if SKF-82958 reduces drug-seeking behaviors in animals exposed previously to cocaine by causing reward-like effects or withdrawal-like aversive effects. OBJECTIVES: Intracranial self-stimulation (ICSS) studies were conducted to determine if SKF-82958 has reward-like or withdrawal-like effects in mice exposed previously to cocaine, or under the influence of cocaine at the time of testing. METHODS: Swiss-Webster mice with lateral hypothalamic stimulating electrodes were trained to self-administer rewarding brain stimulation. The mice were tested in a "curve-shift" variant of the ICSS procedure after intraperitoneal administration of cocaine alone (2.5-20 mg/kg), SKF-82958 alone (0.03-0.3 mg/kg), or a mixture of both drugs (SKF 0.03 mg/kg + 2.5 or 5.0 mg/kg cocaine). Each treatment was given twice. RESULTS: Cocaine and SKF-82958 each caused dose-dependent decreases in brain stimulation reward thresholds that were largest immediately after administration. A dose of SKF-82958 with no reward-related effects of its own potentiated the reward-related effects of low doses of cocaine. Repeated administration did not cause progressive changes in the ability of any treatment to decrease thresholds. CONCLUSIONS: Cocaine and SKF-82958 each potentiate the rewarding effects of lateral hypothalamic brain stimulation in Swiss-Webster mice, implying that these drugs have rewarding effects of their own. The reward-facilitating effects of low doses of cocaine and SKF-82958 are additive (or synergistic). These data suggest that SKF-82958 may decrease cocaine-seeking behavior by mechanisms related to reward rather than aversion.

Animals↗
PubMed2003

Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat.

RATIONALE: Bupropion is an atypical antidepressant and the only non-nicotine-based therapy approved for smoking cessation. Its use has raised much debate as to how a non-nicotine-based agent can aid in smoking cessation. OBJECTIVES: We assessed the effects of bupropion on brain reward function under baseline conditions and subsequent to withdrawal from chronic nicotine administration in rats. METHODS: A discrete-trial intracranial self-stimulation paradigm procedure was used that provides one with current intensity thresholds, a measure of reward in rats under baseline conditions and subsequent to withdrawal from chronic nicotine (3.16 mg/kg per day for 7 days via osmotic minipump). Somatic signs were recorded based on a checklist of nicotine abstinence signs in animals withdrawn from nicotine. RESULTS: Bupropion (10-60 mg/kg) dose-dependently lowered reward thresholds in non-withdrawing subjects indicating an increase in reward. Interestingly, a sub-effective dose of bupropion (5 mg/kg) blocked completely the threshold lowering effects of acute nicotine (0.25 mg/kg). Animals withdrawn from chronic nicotine exhibited increases in somatic signs of withdrawal and elevated brain reward thresholds, which is indicative of "diminished interest or pleasure" (i.e. anhedonia) in the rewarding stimuli. Bupropion (10-40 mg/kg) reversed both the reward deficit and the somatic signs, with the highest dose (40 mg/kg) inducing a protracted reversal of the threshold elevation. CONCLUSIONS: Bupropion acts on multiple levels to alter brain reward circuits influenced by nicotine, in addition to reducing the expression of somatic signs of withdrawal. First, bupropion, unlike other antidepressants, increases brain reward function under baseline conditions in non-withdrawing subjects. Second, at low doses bupropion blocks the rewarding effects of nicotine. Third, bupropion reverses the negative affective aspects of nicotine withdrawal. Such actions are likely to act in concert to mediate the unique anti-smoking properties of bupropion.

Animals↗
PubMed2005

Relative reward processing in primate striatum.

Rewards are often not only valued according to their physical characteristics but also relative to other available rewards. The striatum (caudate nucleus, putamen, ventral striatum including nucleus accumbens) is involved in the organization of movement and the processing of reward information. We studied the activity of single striatal neurons in macaques that were presented with different combinations of two rewards. We found in nearly half of the investigated neurons that the processing for one reward shifted, relative to the other rewards that were available in a given trial block. The relative reward processing concerned all forms of striatal activity related to reward-predicting visual stimuli, arm movements and reception of rewards. The observed changes may provide a neural basis for the known shifts in valuation of rewarding outcomes relative to known references.

Animals↗
PubMed2000

The medial prefrontal cortex as a part of the brain reward system.

This review will briefly summarize experimental evidence for an involvement of the medial prefrontal cortex (mPFC) in reward-related mechanisms in the rat brain. The mPFC is part of the mesocorticolimbic dopaminergic system. It receives prominent dopaminergic input from the ventral tegmental area (VTA) and, via the mediodorsal thalamus, inputs from other subcortical basal ganglia structures. In turn it projects back to the VTA and the nucleus accumbens septi (NAS), which are generally considered as main components of the brain reward system. Evidence for the involvement of the mPFC in reward-related mechanisms comes mainly from three types of studies, conditioned place preference (CPP), intracranial self-stimulation (ICSS), and self-administration. Work will be summarized that has shown that certain drugs injected into the mPFC can produce CPP or that lesions of the mPFC can disrupt the development of CPP, that ICSS is obtained with the stimulating electrode placed in the mPFC, and that certain drugs are self-administered into the mPFC or that lesions of the mPFC disrupt the peripheral self-administration of certain drugs. However, it has also been shown that the role of the mPFC in reward is not uniform. For example, the mPFC appears to be particularly important for the rewarding actions of cocaine, while it appears not to be important for the rewarding actions of amphetamine. Also, different subareas of the mPFC appear to be differentially involved in the rewarding actions of different drugs. Taken together, the available evidence shows that some drugs can produce reward directly within the mPFC, and that some drugs, even though not having direct rewarding effects within the mPFC, depend on the function of the mPFC for the mediation of their rewarding effects.

Animals↗