The '''mesolimbic pathway''', sometimes referred to as the '''reward pathway''', is a [[dopaminergic pathway]] in the [[brain]].<ref name="pmid21205279">{{cite journal | vauthors = Dreyer JL | title = New insights into the roles of microRNAs in drug addiction and neuroplasticity | journal = Genome Med | volume = 2 | issue = 12 | pages = 92 | year = 2010 | pmid = 21205279 | pmc = 3025434 | doi = 10.1186/gm213 | url = }}</ref> The pathway connects the [[ventral tegmentum|ventral tegmental area]] in the [[midbrain]], to the [[ventral striatum]] of the [[basal ganglia]] in the [[forebrain]]. The ventral striatum includes the [[nucleus accumbens]] and the [[olfactory tubercle]].<ref name="Dopaminergic pathways and reward system review">{{cite journal | vauthors = Ikemoto S | title = Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory | journal = Neurosci Biobehav Rev | volume = 35 | issue = 2 | pages = 129–50 | year = 2010 | pmid = 20149820 | pmc = 2894302 | doi = 10.1016/j.neubiorev.2010.02.001 | quote = Recent studies on intracranial self-administration of neurochemicals (drugs) found that rats learn to self-administer various drugs into the mesolimbic dopamine structures–the posterior ventral tegmental area, medial shell nucleus accumbens and medial olfactory tubercle.&nbsp;... In the 1970s it was recognized that the olfactory tubercle contains a striatal component, which is filled with GABAergic medium spiny neurons receiving glutamatergic inputs form cortical regions and dopaminergic inputs from the VTA and projecting to the ventral pallidum just like the nucleus accumbens}}<br />[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894302/figure/F3/ Figure 3: The ventral striatum and self-administration of amphetamine]</ref> The release of dopamine from the mesolimbic pathway into the nucleus accumbens regulates [[incentive salience]] (i.e., motivation and desire for [[rewarding stimuli]]) and facilitates [[reinforcement]] and reward-related motor function learning;<ref name="NAcc function" /><ref name="Malenka NAcc">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-148127-4 | page = 266 | edition = 2nd | chapter = Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu | quote = Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward.}}</ref><ref name="Pleasure system" /> it may also play a role in the subjective perception of [[pleasure]].<ref name="NAcc function">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-148127-4 | pages = 147–148, 367, 376 | edition = 2nd | quote= VTA DA neurons play a critical role in motivation, reward-related behavior (Chapter 15), attention, and multiple forms of memory. This organization of the DA system, wide projection from a limited number of cell bodies, permits coordinated responses to potent new rewards. Thus, acting in diverse terminal fields, dopamine confers motivational salience (“wanting”) on the reward itself or associated cues (nucleus accumbens shell region), updates the value placed on different goals in light of this new experience (orbital prefrontal cortex), helps consolidate multiple forms of memory (amygdala and hippocampus), and encodes new motor programs that will facilitate obtaining this reward in the future (nucleus accumbens core region and dorsal striatum). In this example, dopamine modulates the processing of sensorimotor information in diverse neural circuits to maximize the ability of the organism to obtain future rewards.&nbsp;...<br />The brain reward circuitry that is targeted by addictive drugs normally mediates the pleasure and strengthening of behaviors associated with natural reinforcers, such as food, water, and sexual contact. Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is stimulated by the presence of natural reinforcers, such as food, water, or a sexual partner.&nbsp;...<br />The NAc and VTA are central components of the circuitry underlying reward and memory of reward. As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is involved in learning associated with reinforcement and the modulation of motoric responses to stimuli that satisfy internal homeostatic needs. The shell of the NAc appears to be particularly important to initial drug actions within reward circuitry; addictive drugs appear to have a greater effect on dopamine release in the shell than in the core of the NAc.}}</ref><ref name="Pleasure system">{{cite journal | vauthors = Berridge KC, Kringelbach ML | title = Pleasure systems in the brain | journal = Neuron | volume = 86 | issue = 3 | pages = 646–664 | date = May 2015 | pmid = 25950633 | doi = 10.1016/j.neuron.2015.02.018 | quote = To summarize: the emerging realization that many diverse pleasures share overlapping brain substrates; better neuroimaging maps for encoding human pleasure in orbitofrontal cortex; identification of hotspots and separable brain mechanisms for generating ‘liking’ and ‘wanting’ for the same reward; identification of larger keyboard patterns of generators for desire and dread within NAc, with multiple modes of function; and the realization that dopamine and most ‘pleasure electrode’ candidates for brain hedonic generators probably did not cause much pleasure after all.| pmc=4425246}}</ref> The dysregulation of the mesolimbic pathway and its output neurons in the nucleus accumbens plays a significant role in the development and maintenance of an [[addiction]].<ref name="pmid21205279" /><ref name="Nestler">{{cite journal|vauthors=Robison AJ, Nestler EJ|date=November 2011|title=Transcriptional and epigenetic mechanisms of addiction|journal=Nat. Rev. Neurosci.|volume=12|issue=11|pages=623–637|doi=10.1038/nrn3111|pmc=3272277|pmid=21989194|quote=ΔFosB has been linked directly to several addiction-related behaviors&nbsp;... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states.}}</ref><ref name="ΔFosB reward">{{cite journal|vauthors=Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M|year=2012|title=Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms|journal=Journal of Psychoactive Drugs|volume=44|issue=1|pages=38–55|doi=10.1080/02791072.2012.662112|pmc=4040958|pmid=22641964|quote=It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus. Next, the induction of c-Fos, a downstream (repressed) target of DeltaFosB, was measured in sexually experienced and naive animals. The number of mating-induced c-Fos-IR cells was significantly decreased in sexually experienced animals compared to sexually naive controls. Finally, DeltaFosB levels and its activity in the NAc were manipulated using viral-mediated gene transfer to study its potential role in mediating sexual experience and experience-induced facilitation of sexual performance. Animals with DeltaFosB overexpression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of DeltaJunD, a dominant-negative binding partner of DeltaFosB, attenuated sexual experience-induced facilitation of sexual performance, and stunted long-term maintenance of facilitation compared to DeltaFosB overexpressing group. Together, these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance.&nbsp;... both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry.}}</ref><ref name="Natural and drug addictions">{{cite journal|author=Olsen CM|date=December 2011|title=Natural rewards, neuroplasticity, and non-drug addictions|url=|journal=Neuropharmacology|volume=61|issue=7|pages=1109–22|doi=10.1016/j.neuropharm.2011.03.010|pmc=3139704|pmid=21459101}}</ref>