Nucleus accumbens
Other efferents from the nucleus accumbens include connections with the tail of the ventral tegmental area,[24] substantia nigra, and the reticular formation of the pons.[27][28][29] Function: The shell of the nucleus accumbens is involved in the cognitive processing of reward, including subjective "liking" reactions to certain pleasurable stimuli, motivational salience, and positive reinforcement.[4][5][30][31] That NAcc shell has also been shown to mediate specific Pavlovian-instrumental transfer, a phenomenon in which a classically conditioned stimulus modifies operant behavior.[11][12][13] The NAcc core has also been shown to mediate general Pavlovian-instrumental transfer, a phenomenon in which a classically conditioned stimulus modifies operant behavior.A recent study demonstrated that suppression of the glucocorticoid receptors led to a decrease in the release of dopamine, which may lead to future research involving anti-glucocorticoid drugs to potentially relieve psychotic symptoms.[27][41] Glutamate: Studies have shown that local blockade of glutamatergic NMDA receptors in the NAcc core impaired spatial learning.[42] Another study demonstrated that both NMDA and AMPA (both glutamate receptors) play important roles in regulating instrumental learning.[45] Substantial evidence from pharmacological manipulation also suggests that reducing the excitability of neurons in the nucleus accumbens is rewarding, as, for example, would be true in the case of μ-opioid receptor stimulation.[30] The regions of the nucleus accumbens that can be ascribed a causal role in the production of pleasure are limited both anatomically and chemically, as besides opioid agonists only endocannabinoids can enhance liking.In the nucleus accumbens as a whole, dopamine, GABA receptor agonist or AMPA antagonists solely modify motivation, while the same is true for opioid and endocannabinoids outside of the hotspot in the medial shell.One task where the effect of NAcc lesions is evident is Pavlovian-instrumental transfer (PIT), where a cue paired with a specific or general reward can enhance instrumental responding.[55] An fMRI study conducted in 2005 found that when mother rats were in the presence of their pups the regions of the brain involved in reinforcement, including the nucleus accumbens, were highly active.[6] In late 2017, studies on rodents which utilized optogenetic and chemogenetic methods found that the indirect pathway (i.e., D2-type) medium spiny neurons in the nucleus accumbens core which co-express adenosine A2A receptors and project to the ventral pallidum are involved in the regulation of slow-wave sleep.[12][13] In contrast, the D2-type medium spiny neurons in the NAcc shell which express adenosine A2A receptors have no role in regulating slow-wave sleep.[20][35][61] ΔFosB overexpression has been implicated in addictions to alcohol (ethanol), cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol, and substituted amphetamines, among others.[20] ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.[27][38] In April 2007, two research teams reported on having inserted electrodes into the nucleus accumbens in order to use deep brain stimulation to treat severe depression.[65] In 2010, experiments reported that deep brain stimulation of the nucleus accumbens was successful in decreasing depression symptoms in 50% of patients who did not respond to other treatments such as electroconvulsive therapy.
Mesolimbic pathwayBasal gangliaVentral striatumNeuroNamesNeuroLexAnatomical terms of neuroanatomynucleusseptumbasal forebrainpreoptic areahypothalamusolfactory tubercledorsal striatumstriatumdopaminergic neuronsGABAergicmedium spiny neuronscerebral hemisphereD1-typeD2-typecognitive functionsmotivationaversionrewardincentive saliencepleasurepositive reinforcementreinforcementPavlovian-instrumental transferaddictionslow-wave sleepimpulsivityplacebo effectmotor programsglutamatergicprefrontal cortexprelimbic cortexinfralimbic cortexbasolateral amygdalahippocampusthalamicmidline thalamic nucleiintralaminar nuclei of the thalamusventral tegmental areadopaminergic inputscortico-basal ganglia-thalamo-cortical loopeuphoriantamphetamineopiatessubiculumdorsomedialtuberomammillary nucleushistamineaxonal projectionsglobus pallidusventral pallidummedial dorsal nucleusthalamustail of the ventral tegmental areasubstantia nigrareticular formationextended amygdaladopamine receptorsdendritic spinespleasurable stimulimotivational saliencespecific Pavlovian-instrumental transferclassically conditioned stimulusoperant behaviorAddictive drugsGABA receptorsmotor functionadenosine A2A receptorsgeneral Pavlovian-instrumental transfercholinergicinterneuronsDopaminerewarding stimulirecreational drugssubstituted amphetaminescocainenicotinemorphinePhenethylaminetyraminetrace aminesaromatic amino acid hydroxylaseenzymeneuromodulatorsGlucocorticoidcorticosteroidL-DOPAsteroidsGABAA receptorsGABAB receptorsacetylcholineGlutamateNMDA receptorsglutamate receptorsSerotoninsucrosequinineμ-opioid receptorblood oxygen level dependent signal (BOLD)δ-opioid agonistsκ-opioid agonistsendocannabinoidsGABA receptor agonistorbitofrontal cortex (OFC)infralimbicenhancing locomotionaversivereducing locomotionoptogeneticchemogeneticgene expressionmesocorticolimbic projectiontranscription factorsΔFosBnecessary and sufficientself-administrationreward sensitizationalcohol (ethanol)cannabinoidsmethylphenidateopioids