Reward system
[1][4] The reward system motivates animals to approach stimuli or engage in behaviour that increases fitness (sex, energy-dense foods, etc.).Reward cognition serves to increase the likelihood of survival and reproduction by causing associative learning, eliciting approach and consummatory behavior, and triggering positively-valenced emotions.[2] In neuroscience, the reward system is a collection of brain structures and neural pathways that are responsible for reward-related cognition, including associative learning (primarily classical conditioning and operant reinforcement), incentive salience (i.e., motivation and "wanting", desire, or craving for a reward), and positively-valenced emotions, particularly emotions that involve pleasure (i.e., hedonic "liking").[1][3] Reward related activities, such as feeding, exercise, sex, substance use, and social interactions play a factor in elevated levels of dopamine, ultimately altering the CNS (or the central nervous system).[3][11][13][14][15] The dorsal raphe nucleus and cerebellum appear to modulate some forms of reward-related cognition (i.e., associative learning, motivational salience, and positive emotions) and behaviors as well.[11] The glutamatergic projection nuclei in the subthalamic nucleus, prefrontal cortex, hippocampus, thalamus, and amygdala connect to other parts of the reward system via glutamate pathways.While GABA receptor agonists are capable of eliciting both "liking" and "wanting" reactions in the nucleus accumbens, glutaminergic inputs from the basolateral amygdala, ventral hippocampus, and medial prefrontal cortex can drive incentive salience.[5][27][28] Third, when animals are administered addictive drugs or engage in naturally rewarding behaviors, such as feeding or sexual activity, there is a marked release of dopamine within the nucleus accumbens.[2][40][41] The degree of dopamine neurotransmission into the NAcc shell from the mesolimbic pathway is highly correlated with the magnitude of incentive salience for rewarding stimuli.In the NAcc, such a dichotomy is not as clear cut, and activation of both D1 and D2 MSNs is sufficient to enhance motivation,[45][46] likely via disinhibiting the VTA through inhibiting the ventral pallidum.[47][48] Robinson and Berridge's 1993 incentive-sensitization theory proposed that reward contains separable psychological components: wanting (incentive) and liking (pleasure).Although classical conditioning is not limited to the reward system, the enhancement of instrumental performance by stimuli (i.e., Pavlovian-instrumental transfer) requires the nucleus accumbens.[51] During instrumental learning, opposing changes in the ratio of AMPA to NMDA receptors and phosphorylated ERK occurs in the D1-type and D2-type MSNs that constitute the direct and indirect pathways, respectively.The intracellular cascade activated by D1 receptors involves the recruitment of protein kinase A, and through resulting phosphorylation of DARPP-32, the inhibition of phosphatases that deactivate ERK.Rats also learn to lever-press for cocaine injections into the medial prefrontal cortex, which works by increasing dopamine turnover in the nucleus accumbens.[69][70] Nicotine infused directly into the nucleus accumbens also enhances local dopamine release, presumably by a presynaptic action on the dopaminergic terminals of this region.[71][72] Some additional habit-forming drugs are also likely to decrease the output of medium spiny neurons as a consequence, despite activating dopaminergic projections.Anhedonia, traditionally defined as a reduced capacity to feel pleasure, has been re-examined as reflecting blunted incentive salience, as most anhedonic populations exhibit intact "liking".[80] Reduced activity in the mPFC during reward related tasks appears to be localized to more dorsal regions(i.e. the pregenual cingulate cortex), while the more ventral sgACC is hyperactive in depression.CMS similarly reduces sucrose preference, and behavioral despair as assessed by tail suspension and forced swim tests.They discovered that rats would perform behaviors such as pressing a bar, to administer a brief burst of electrical stimulation to specific sites in their brains.Typically, rats will press a lever hundreds or thousands of times per hour to obtain this brain stimulation, stopping only when they are exhausted.The explanation to why animals engage in a behavior that has no value to the survival of either themselves or their species is that the brain stimulation is activating the system underlying reward.[93] In a fundamental discovery made in 1954, researchers James Olds and Peter Milner found that low-voltage electrical stimulation of certain regions of the brain of the rat acted as a reward in teaching the animals to run mazes and solve problems.[98] More recently, Ivan De Araujo and colleagues used nutrients inside the gut to stimulate the reward system via the vagus nerve.[99] Animals quickly learn to press a bar to obtain an injection of opiates directly into the midbrain tegmentum or the nucleus accumbens.[101][102] This research demonstrated that increased dopamine neurotransmission acts as a sine qua non condition for pleasurable hedonic reactions to music in humans.
incentive saliencemotivationassociative learningpositive reinforcementclassical conditioningpositively-valencedemotionspleasureeuphoriaecstasyoperant conditioningpositive reinforcersaddictionsurvival of one's self and offspringpalatable foodsexual contactparental investmentlearned associationclassically conditioned(more unsolved problems in biology)operant reinforcementmotivational saliencecortico-basal ganglia-thalamo-cortical loopbasal gangliaglutamatergicinterneuronsGABAergicmedium spiny neuronsdopaminergicprojection neuronsorexinergicventral tegmental areaventral striatumnucleus accumbensolfactory tubercledorsal striatumcaudate nucleusputamensubstantia nigrapars compactapars reticulataprefrontal cortexanterior cingulate cortexinsular cortexhippocampushypothalamuslateral hypothalamusthalamussubthalamic nucleusglobus pallidusexternalinternalventral pallidumparabrachial nucleusamygdalaextended amygdaladorsal raphe nucleuscerebellumpositive emotionslaterodorsal tegmental nucleus (LDT)pedunculopontine nucleus (PPTg)lateral habenula (LHb)rostromedial tegmental nucleus (RMTg)aversive saliencedopamine pathwaysneurotransmitterdopamineD1-like receptorsD2-like receptorsstriatummedial forebrain bundlebrain stimulation rewardGABA receptoragonistsbasolateral amygdalaintracranial self-stimulationmesolimbic dopamine pathwaynatural rewardsdrug rewardperipheral nervesmesolimbic pathwaytyrosinetyrosine hydroxylaseDOPA decarboxylaseflashbulb memoriesnucleus accumbens shellorbitofrontal cortexopioidsendocannabinoidsorexininduced expressionimmediate early genedopaminergic pathwayslearningclassical conditioning (Pavlovian conditioning)operant conditioning (instrumental conditioning)reinforcergoal-directedhabitsPavlovian-instrumental transferdirect and indirect pathwaysprotein kinase ADARPP-32Ras-Raf-MEK-ERK pathwayΔFosBgene transcription factoroverexpressionD1-typebehavioral addictionsdrug addictionsneural plasticityself-administrationreward sensitizationepigenetichistoneaddictionsAddictive drugsbehaviorsreinforcingdopamine reward pathwayefferentmedial prefrontal cortexAnhedoniasubgenual cingulate cortex (sgACC)pregenual cingulate cortexOptogenetic