Мезолімбічний шлях (лат. tractus mesolimbicus, англ. mesolimbic pathway), іноді також «шлях винагороди» (англ. reward pathway) — це [en] у мозку, що сполучає вентральну область покришки в середньому мозку та вентральне смугасте тіло базальних ганглій у передньому мозку. Вентральне смугасте тіло включає прилегле ядро та нюховий горбок.
Виділення допаміну з мезолімбічного шляху в прилегле ядро регулює [en] (наприклад, бажання стимулювати винагороду) та сприяє підкріпленню та пов'язаному з винагородою навчанню рухових функцій. Також може грати роль у суб'єктивному сприйнятті насолоди. Порушення регуляції мезолімбічного шляху та його вихідних нейронів у прилеглому ядрі відіграє значну роль у розвитку та підтримці залежності.
Примітки
- Dreyer JL (2010). New insights into the roles of microRNAs in drug addiction and neuroplasticity. Genome Med. 2 (12): 92. doi:10.1186/gm213. PMC 3025434. PMID 21205279.
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: Обслуговування CS1: Сторінки із непозначеним DOI з безкоштовним доступом () - Ikemoto S (2010). Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory. Neurosci Biobehav Rev. 35 (2): 129—50. doi:10.1016/j.neubiorev.2010.02.001. PMC 2894302. PMID 20149820.
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. ... 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
Figure 3: The ventral striatum and self-administration of amphetamine - Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY (ред.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (вид. 2nd). New York: McGraw-Hill Medical. с. 147—148, 367, 376. ISBN .
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. ...
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. ...
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. - Malenka RC, Nestler EJ, Hyman SE (2009). Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu. У Sydor A, Brown RY (ред.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (вид. 2nd). New York: McGraw-Hill Medical. с. 266. ISBN .
Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward.
- Berridge KC, Kringelbach ML (May 2015). Pleasure systems in the brain. Neuron. 86 (3): 646—664. doi:10.1016/j.neuron.2015.02.018. PMC 4425246. PMID 25950633.
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.
- Robison AJ, Nestler EJ (November 2011). Transcriptional and epigenetic mechanisms of addiction. Nat. Rev. Neurosci. 12 (11): 623—637. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194.
ΔFosB has been linked directly to several addiction-related behaviors ... 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.
- Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (2012). Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms. Journal of Psychoactive Drugs. 44 (1): 38—55. doi:10.1080/02791072.2012.662112. PMC 4040958. PMID 22641964.
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. ... 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.
- Olsen CM (December 2011). Natural rewards, neuroplasticity, and non-drug addictions. Neuropharmacology. 61 (7): 1109—22. doi:10.1016/j.neuropharm.2011.03.010. PMC 3139704. PMID 21459101.
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Mezolimbichnij shlyah lat tractus mesolimbicus angl mesolimbic pathway inodi takozh shlyah vinagorodi angl reward pathway ce en u mozku sho spoluchaye ventralnu oblast pokrishki v serednomu mozku ta ventralne smugaste tilo bazalnih ganglij u perednomu mozku Ventralne smugaste tilo vklyuchaye prilegle yadro ta nyuhovij gorbok Vidilennya dopaminu z mezolimbichnogo shlyahu v prilegle yadro regulyuye en napriklad bazhannya stimulyuvati vinagorodu ta spriyaye pidkriplennyu ta pov yazanomu z vinagorodoyu navchannyu ruhovih funkcij Takozh mozhe grati rol u sub yektivnomu sprijnyatti nasolodi Porushennya regulyaciyi mezolimbichnogo shlyahu ta jogo vihidnih nejroniv u prileglomu yadri vidigraye znachnu rol u rozvitku ta pidtrimci zalezhnosti PrimitkiDreyer JL 2010 New insights into the roles of microRNAs in drug addiction and neuroplasticity Genome Med 2 12 92 doi 10 1186 gm213 PMC 3025434 PMID 21205279 a href wiki D0 A8 D0 B0 D0 B1 D0 BB D0 BE D0 BD Cite journal title Shablon Cite journal cite journal a Obslugovuvannya CS1 Storinki iz nepoznachenim DOI z bezkoshtovnim dostupom posilannya Ikemoto S 2010 Brain reward circuitry beyond the mesolimbic dopamine system a neurobiological theory Neurosci Biobehav Rev 35 2 129 50 doi 10 1016 j neubiorev 2010 02 001 PMC 2894302 PMID 20149820 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 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 Figure 3 The ventral striatum and self administration of amphetamine Malenka RC Nestler EJ Hyman SE 2009 Sydor A Brown RY red Molecular Neuropharmacology A Foundation for Clinical Neuroscience vid 2nd New York McGraw Hill Medical s 147 148 367 376 ISBN 978 0 07 148127 4 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 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 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 Malenka RC Nestler EJ Hyman SE 2009 Chapter 10 Neural and Neuroendocrine Control of the Internal Milieu U Sydor A Brown RY red Molecular Neuropharmacology A Foundation for Clinical Neuroscience vid 2nd New York McGraw Hill Medical s 266 ISBN 978 0 07 148127 4 Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward Berridge KC Kringelbach ML May 2015 Pleasure systems in the brain Neuron 86 3 646 664 doi 10 1016 j neuron 2015 02 018 PMC 4425246 PMID 25950633 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 Robison AJ Nestler EJ November 2011 Transcriptional and epigenetic mechanisms of addiction Nat Rev Neurosci 12 11 623 637 doi 10 1038 nrn3111 PMC 3272277 PMID 21989194 DFosB has been linked directly to several addiction related behaviors Importantly genetic or viral overexpression of DJunD a dominant negative mutant of JunD which antagonizes DFosB and other AP 1 mediated transcriptional activity in the NAc or OFC blocks these key effects of drug exposure14 22 24 This indicates that DFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure DFosB 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 DFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive like states Blum K Werner T Carnes S Carnes P Bowirrat A Giordano J Oscar Berman M Gold M 2012 Sex drugs and rock n roll hypothesizing common mesolimbic activation as a function of reward gene polymorphisms Journal of Psychoactive Drugs 44 1 38 55 doi 10 1080 02791072 2012 662112 PMC 4040958 PMID 22641964 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 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 Olsen CM December 2011 Natural rewards neuroplasticity and non drug addictions Neuropharmacology 61 7 1109 22 doi 10 1016 j neuropharm 2011 03 010 PMC 3139704 PMID 21459101