Nucleus accumbens

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Nucleus accumbens
Gray727-Brodman.png
Medial surface, person facing to the left. Nucleus accumbens is very roughly in Brodmann area 34
Details
Latin nucleus accumbens septi
Part of Mesolimbic pathway
Basal ganglia (Ventral striatum)
Components Nucleus accumbens shell
Nucleus accumbens core
Identifiers
Acronym(s) NAc or NAcc
MeSH A08.186.211.730.885.105.683
NeuroNames hier-259
NeuroLex ID Nucleus accumbens
Dorlands
/Elsevier
n_11/12580142
TA A14.1.09.440
FMA FMA:61889
Anatomical terms of neuroanatomy

The nucleus accumbens (NAc or NAcc), also known as the accumbens nucleus or as the nucleus accumbens septi (Latin for nucleus adjacent to the septum) is a region in the basal forebrain rostral to the preoptic area of the hypothalamus.[1] The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum, which is part of the basal ganglia.[2]

The nucleus accumbens has a significant role in the cognitive processing of motivation, pleasure, and reward and reinforcement learning, and hence has significant role in addiction.[3][4] It plays a lesser role in fear, impulsivity, and the placebo effect.[5][6][7] It is involved in the encoding of new motor programs as well.[3]

Each cerebral hemisphere has its own nucleus accumbens. It is located where the head of the caudate and the anterior portion of the putamen meet just lateral to the septum pellucidum. The nucleus accumbens can be divided into two structures—the nucleus accumbens core and the nucleus accumbens shell. These structures have different morphology and function.


Structure[edit]

The nucleus accumbens is an aggregate of neurons which is described as having an outer shell and an inner core.[3]


Input[edit]

Major inputs to the nucleus accumbens include prefrontal association cortices, basolateral amygdala, and dopaminergic neurons located in the ventral tegmental area (VTA), which connect via the mesolimbic pathway. Thus the nucleus accumbens is often described as one part of a cortico-striato-thalamo-cortical loop.

Dopaminergic input from the VTA modulate the activity of neurons within the nucleus accumbens. These neurons are activated directly or indirectly by euphoriant drugs (e.g., amphetamine, opiates, nicotine, etc.) and by participating in rewarding experiences (e.g., sex, music, exercise, etc.).[8][9]

Another major source of input comes from the CA1 and ventral subiculum of the hippocampus to the dorsomedial area of the nucleus accumbens. The neurons of the hippocampus have a noteworthy correlation to slight depolarizations of cells in the nucleus accumbens, which makes them more positive and therefore more excitable. The correlated cells of these excited states of the medium spiny neurons in the nucleus accumbens are shared equally between the subiculum and CA1. The subiculum neurons are found to hyperpolarize (increase negativity) while the CA1 neurons "ripple" (fire > 50 Hz) in order to accomplish this priming.[10]

The sole source of histamine neurons in the brain, the tuberomammillary nucleus, projects to the nucleus accumbens as well.[11]

Output[edit]

The output neurons of the nucleus accumbens send axon projections to the basal ganglia and the ventral analog of the globus pallidus, known as the ventral pallidum (VP). The VP, in turn, projects to the medial dorsal nucleus of the dorsal thalamus, which projects to the prefrontal cortex as well as the striatum. Other efferents from the nucleus accumbens include connections with the tail of the ventral tegmental area,[12] substantia nigra, and the reticular formation of the pons.[1]

Shell[edit]

The nucleus accumbens shell is a substructure of the nucleus accumbens. The shell and core together form the entire nucleus accumbens.

Location: The shell is the outer region of the nucleus accumbens, and – unlike the core – is considered to be part of the extended amygdala, located at its rostral pole.

Cell types: Neurons in the nucleus accumbens are mostly medium spiny neurons. The neurons in the shell, as compared to the core, have a lower density of dendritic spines, less terminal segments, and less branch segments than those in the core. The shell neurons project to the subcommissural part of the ventral pallidum as well as the ventral tegmental area and to extensive areas in the hypothalamus and extended amygdala.[13][14][15]

Function: The shell of the nucleus accumbens is involved in the cognitive processing of motivational salience (wanting) as well as reward and reinforcement effects.[3] Particularly important are the effects of drug and naturally rewarding stimuli on the NAc shell because these effects are related to addiction.[3] Addictive drugs have a larger effect on dopamine release in the shell than in the core.[3]

Core[edit]

The nucleus accumbens core is the inner substructure of the nucleus accumbens.

Location: The nucleus accumbens core is part of the ventral striatum, located within the basal ganglia.

Cell types: The core of the NAcc is made up mainly of medium spiny neurons. The neurons in the core, as compared to the neurons in the shell, have an increased density of dendritic spines, branch segments, and terminal segments. From the core, the neurons project to other sub-cortical areas such as the globus pallidus and the substantia nigra. GABA is one of the main neurotransmitters in the NAcc, and GABA receptors are also abundant.[16][17]

Function: The nucleus accumbens core is involved in the cognitive processing of motor function related to reward and reinforcement.[3] Specifically, the core encodes new motor programs which facilitate the acquisition of a given reward in the future.[3]

Cell types[edit]

The core of the NAcc is made up mainly of medium spiny neurons. Compared to the neurons in the shell, those in the core have an increased density of dendritic spines, branch segments, and terminal segments. From the core, the neurons project to other sub-cortical areas such as the globus pallidus and the substantia nigra. GABA is one of the main neurotransmitters in the NAcc, and GABA receptors are also abundant.[16][18] These neurons are also the main projection or output neurons of the nucleus accumbens.

While 95% of the neurons projecting from the nucleus accumbens are medium spiny GABA-ergic neurons, other projecting neuronal types are also present, such as large cholinergic interneurons.

Neurotransmitters[edit]

Dopamine: Dopamine is related to recreational drugs including amphetamines, cocaine, and morphine, which increase extracellular levels of dopamine in both the NAc shell and the NAc core, but the effect of these increases is more pronounced in the shell. Only amphetamine at high levels increased extracellular levels of dopamine to similar levels in both the shell and the core. All of this points to a 'functional heterogeneity' in the nucleus accumbens between the shell region and the core region.[19] Similarly to drug rewards, non-drug rewards also increase levels of extracellular dopamine in the NAc shell, but drug induced DA increase is more resilient to habituation when exposed repeatedly to drug-stimuli, unlike non-drug rewarding stimuli induced dopamine increases, which do succumb to habituation. Recent[when?] studies have shown that the repeated influence of drug-inducing DA projection has an abnormal strengthening effect on stimulus-drug associations and increases the drug-reward stimuli’s resistance to extinction. This may be a contributing factor to addiction. This effect was more pronounced in the NAc shell than in the NAc core.[13][13][20]

Phenethylamine and tyramine: Phenethylamine and tyramine are trace amine compounds which are synthesized in several types of CNS neurons, including all dopamine neurons.[21] Specifically, these neurotransmitters act within the dopaminergic inputs to the NAcc. These substances regulate the presynaptic release of dopamine through their interactions with VMAT2 and TAAR1, analogous to amphetamine.

Glucocorticoids and dopamine: Glucocorticoid receptors are the only corticosteroid receptors in the nucleus accumbens shell. L-DOPA, steroids, and specifically glucocorticoids are currently known to be the only known endogenous compounds that can induce psychotic problems, so understanding the hormonal control over dopaminergic projections with regards to glucocorticoid receptors could lead to new treatments for psychotic symptoms. 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.[22]

GABA: A recent study on rats that used GABA agonists and antagonists indicated that GABAA receptors in the NAc shell have inhibitory control on turning behavior influenced by dopamine, and GABAB receptors have inhibitory control over turning behavior mediated by acetylcholine.[13][23]

Glutamate: Studies have shown that local blockade of glutamatergic NMDA receptors in the NAcc core impaired spatial learning.[24] Another study demonstrated that both NMDA and AMPA (both glutamate receptors) play important roles in regulating instrumental learning.[25]

Serotonin (5-HT): Overall, 5-HT synapses are more abundant and have a greater number of synaptic contacts in the NAc shell than in the core. They are also larger and thicker, and contain more large dense core vesicles than their counterparts in the core.

Function[edit]

Reward and reinforcement[edit]

The nucleus accumbens, being one part of the reward system, plays an important role in processing rewarding stimuli, reinforcing stimuli (e.g., food and water), and those which are both rewarding and reinforcing (addictive drugs, sex, and exercise).[3][26] The nucleus accumbens is selectively activated during the perception of pleasant, emotionally arousing pictures and during mental imagery of pleasant, emotional scenes.[27][28] A 2005 study found that it is involved in the regulation of emotions induced by music,[29] perhaps consequent to its role in mediating dopamine release. The nucleus accumbens plays a role in rhythmic timing and is considered to be of central importance to the limbic-motor interface (Mogensen).[citation needed]

In the 1950s, James Olds and Peter Milner implanted electrodes into the septal area of the rat and found that the rat chose to press a lever which stimulated it. It continued to prefer this even over stopping to eat or drink. This suggests that the area is the "pleasure center" of the brain and is involved in reinforcement learning.[30] In rats, stimulation of the ventral tegmental area causes the release of dopamine in the nucleus accumbens much in the same way as addictive drugs and natural reinforcers, such as water or food, initiate the release of dopamine in the nucleus accumbens.[31] The same results have been seen in human subjects in functional imaging studies. For example, increased dopamine concentration is seen in the extracellular fluid of the nucleus accumbens when subjects believed they were being given money[citation needed], and increased activation (i.e., increased fMRI BOLD signal-change) was observed among heterosexual males viewing pictures of attractive women.[32]

Maternal behavior[edit]

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.[33] Levels of dopamine increase in the nucleus accumbens during maternal behavior, while lesions in this area upset maternal behavior.[34] When human mothers are presented pictures of their children, fMRIs show an increased brain activity in the nucleus accumbens and other reinforcing brain regions and a decrease in activity in areas of the brain involved with negative emotions.[citation needed]

Clinical significance[edit]

Addiction[edit]

Current models of addiction from chronic drug use involve alterations in gene expression in the mesocorticolimbic projection.[8][35][36] The most important transcription factors that produce these alterations are ΔFosB, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and nuclear factor kappa B (NFκB).[8] ΔFosB is the most significant gene transcription factor in addiction since its viral or genetic overexpression in the nucleus accumbens is necessary and sufficient for many of the neural adaptations seen in drug addiction;[8] it has been implicated in addictions to alcohol, cannabinoids, cocaine, nicotine, phenylcyclidine, opiates, and substituted amphetamines.[8][35][37] ΔJunD is the transcription factor which directly opposes ΔFosB.[8] Increases in nucleus accumbens ΔJunD expression can reduce or, with a large increase, even block most of the neural alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).[8]

ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.[8][9] Natural rewards, like drugs of abuse, induce ΔFosB in the nucleus accumbens, and chronic acquisition of these rewards can result in a similar pathological addictive state through ΔFosB overexpression.[8][9][26] Consequently, ΔFosB is the key transcription factor involved in addictions to natural rewards as well;[8][9][26] in particular, ΔFosB in the nucleus accumbens is critical for the reinforcing effects of sexual reward.[9] Research on the interaction between natural and drug rewards suggests that psychostimulants and sexual behavior act on similar biomolecular mechanisms to induce ΔFosB in the nucleus accumbens and possess cross-sensitization effects that are mediated through ΔFosB.[26][38]

Summary of addiction-related plasticity
Form of neural or behavioral plasticity Type of reinforcer Sources
Opiates Psychostimulants High fat or sugar food Sexual reward Exercise Environmental enrichment
ΔFosB expression
in the nucleus accumbens
[26]
Behavioral Plasticity
Escalation of intake Yes Yes Yes [26]
Psychostimulant
cross-sensitization
Yes Not applicable Yes Yes Attenuated Attenuated [26]
Psychostimulant
self-administration
[26]
Psychostimulant
conditioned place preference
[26]
Reinstatement of drug-seeking behavior [26]
Neurochemical Plasticity
CREB phosphorylation
in the nucleus accumbens
[26]
Sensitized dopamine response
in the nucleus accumbens
No Yes No Yes [26]
Altered striatal dopamine signaling DRD2, ↑DRD3 DRD1, ↓DRD2, ↑DRD3 DRD1, ↓DRD2, ↑DRD3 DRD2 DRD2 [26]
Altered striatal opioid signaling μ-opioid receptors μ-opioid receptors
κ-opioid receptors
μ-opioid receptors μ-opioid receptors No change No change [26]
Changes in striatal opioid peptides dynorphin dynorphin enkephalin dynorphin dynorphin [26]
Mesocorticolimbic Synaptic Plasticity
Number of dendrites in the nucleus accumbens [26]
Dendritic spine density in
the nucleus accumbens
No change [26]

Depression[edit]

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.[39] 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.[40] Nucleus accumbens has also been used as a target to treat small groups of patients with therapy-refractory obsessive-compulsive disorder.[41]

Placebo effect[edit]

Activation of the NAcc has been shown to occur in the anticipation of effectiveness of a drug when a user is given a placebo, indicating a contributing role of the nucleus accumbens in the placebo effect.[6][42]

Additional images[edit]

References[edit]

  1. ^ a b Carlson, Neil R. Physiology of Behavior. 11th ed. Boston: Pearson, 2013. Print.
  2. ^ Nucleus Accumbens
  3. ^ a b c d e f g h i Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY, ed. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 147–148, 367, 376. ISBN 9780071481274. 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.
     
  4. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 266. ISBN 9780071481274. Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward. 
  5. ^ Schwienbacher I, Fendt M, Richardson R, Schnitzler HU (2004). "Temporary inactivation of the nucleus accumbens disrupts acquisition and expression of fear-potentiated startle in rats". Brain Res. 1027 (1–2): 87–93. doi:10.1016/j.brainres.2004.08.037. PMID 15494160. 
  6. ^ a b Zubieta JK, Stohler CS (March 2009). "Neurobiological mechanisms of placebo responses". Ann. N. Y. Acad. Sci. 1156: 198–210. doi:10.1111/j.1749-6632.2009.04424.x. PMC 3073412. PMID 19338509. 
  7. ^ Basar K, Sesia T, Groenewegen H, Steinbusch HW, Visser-Vandewalle V, Temel Y (December 2010). "Nucleus accumbens and impulsivity". Prog. Neurobiol. 92 (4): 533–57. doi:10.1016/j.pneurobio.2010.08.007. PMID 20831892. 
  8. ^ a b c d e f g h i j 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. 
  9. ^ a b c d e 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". J. Psychoactive Drugs 44 (1): 38–55. doi:10.1080/02791072.2012.662112. PMC 4040958. PMID 22641964. 
  10. ^ O'Donnell, P., Goto, Y. (2001). "Synchronous activity in the hippocampus and nucleus accumbens in vivo". J. Neurosci. 21 (4): RC131. PMID 11160416. 
  11. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 175–176. ISBN 9780071481274. Within the brain, histamine is synthesized exclusively by neurons with their cell bodies in the tuberomammillary nucleus (TMN) that lies within the posterior hypothalamus. There are approximately 64000 histaminergic neurons per side in humans. These cells project throughout the brain and spinal cord. Areas that receive especially dense projections include the cerebral cortex, hippocampus, neostriatum, nucleus accumbens, amygdala, and hypothalamus.  ... While the best characterized function of the histamine system in the brain is regulation of sleep and arousal, histamine is also involved in learning and memory ... It also appears that histamine is involved in the regulation of feeding and energy balance. 
  12. ^ Barrot M, Sesack SR, Georges F, Pistis M, Hong S, Jhou TC (October 2012). "Braking dopamine systems: a new GABA master structure for mesolimbic and nigrostriatal functions". J. Neurosci. 32 (41): 14094–14101. doi:10.1523/JNEUROSCI.3370-12.2012. PMC 3513755. PMID 23055478. 
  13. ^ a b c d Shirayama, Y; Chaki, S (2006). "Neurochemistry of the Nucleus Accumbens and its Relevance to Depression and Antidepressant Action in Rodents". Current Neuropharmacology 4 (4): 277–291. doi:10.2174/157015906778520773. PMC 2475798. PMID 18654637. 
  14. ^ Meredith, GE; Agolia, R; Arts, MP; Groenewegen, HJ; Zahm, DS (1992). "Morphological differences between projection neurons of the core and shell in the nucleus accumbens of the rat". Neuroscience 50 (1): 149–62. doi:10.1016/0306-4522(92)90389-j. PMID 1383869. 
  15. ^ Meredith, GE; Pennartz, CM; Groenewegen, HJ (1993). "The cellular framework for chemical signalling in the nucleus accumbens". Progress in brain research 99: 3–24. doi:10.1016/s0079-6123(08)61335-7. PMID 7906426. 
  16. ^ a b Shirayama, Yukihiko, and Shigeyuki Chaki. "Neurochemistry of the Nucleus Accumbens and Its Relevance to Depression and Antidepressant Action in Rodents." Current Neuropharmocology 4.4 (2006): 277–91. Bentham Science Publishers Ltd. Web. 16 November 2011. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475798/>.
  17. ^ Meredith, G. E., C. M. Pennartz, and H. J. Groenewegen. "The Cellular Framework for Chemical Signalling in the Nucleus Accumbens." Progress in Brain Research 99 (1993): 3–24. Web. 16 November 2011. <http://www.ncbi.nlm.nih.gov/pubmed/7906426>.
  18. ^ Meredith, G. E., C. M. Pennartz, and H. J. Groenewegen. "The Cellular Framework for Chemical Signalling in the Nucleus Accumbens." Progress in Brain Research 99 (1993): 3–24. Web. 16 November 2011. <http://www.ncbi.nlm.nih.gov/pubmed/7906426>.
  19. ^ Pontieri, FE; Tanda, G; Di Chiara, G (1995). "Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the "shell" as compared with the "core" of the rat nucleus accumbens". Proceedings of the National Academy of Sciences of the United States of America 92 (26): 12304–12308. doi:10.1073/pnas.92.26.12304. PMC 40345. PMID 8618890. 
  20. ^ Di Chiara, G (2002). "Nucleus accumbens shell and core dopamine: Differential role in behavior and addiction". Behavioural Brain Research 137 (1–2): 75–114. doi:10.1016/s0166-4328(02)00286-3. PMID 12445717. 
  21. ^ Eiden LE, Weihe E (January 2011). "VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse". Ann. N. Y. Acad. Sci. 1216: 86–98. doi:10.1111/j.1749-6632.2010.05906.x. PMID 21272013. VMAT2 is the CNS vesicular transporter for not only the biogenic amines DA, NE, EPI, 5-HT, and HIS, but likely also for the trace amines TYR, PEA, and thyronamine (THYR) ... [Trace aminergic] neurons in mammalian CNS would be identifiable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme aromatic amino acid decarboxylase (AADC). 
  22. ^ Barrot, M; Marinelli, M; Abrous, DN; Rougé-Pont, F; Le Moal, M; Piazza, PV (2000). "The dopaminergic hyper-responsiveness of the shell of the nucleus accumbens is hormone-dependent". The European Journal of Neuroscience 12 (3): 973–9. doi:10.1046/j.1460-9568.2000.00996.x. PMID 10762327. 
  23. ^ Akiyama, G; Ikeda, H; Matsuzaki, S; Sato, M; Moribe, S; Koshikawa, N; Cools, AR (2004). "GABAA and GABAB receptors in the nucleus accumbens shell differentially modulate dopamine and acetylcholine receptor-mediated turning behaviour". Neuropharmacology 46 (8): 1082–8. doi:10.1016/j.neuropharm.2004.02.007. PMID 15111014. 
  24. ^ Smith-Roe SL, Sadeghian K, Kelley AE (August 1999). "Spatial learning and performance in the radial arm maze is impaired after N-methyl-D-aspartate (NMDA) receptor blockade in striatal subregions". Behav. Neurosci. 113 (4): 703–17. doi:10.1037/0735-7044.113.4.703. PMID 10495079. 
  25. ^ Giertler C, Bohn I, Hauber W (March 2005). "Involvement of NMDA and AMPA/KA receptors in the nucleus accumbens core in instrumental learning guided by reward-predictive cues". Eur. J. Neurosci. 21 (6): 1689–702. doi:10.1111/j.1460-9568.2005.03983.x. PMID 15845096. 
  26. ^ a b c d e f g h i j k l m n o p q Olsen CM (December 2011). "Natural rewards, neuroplasticity, and non-drug addictions". Neuropharmacology 61 (7): 1109–1122. doi:10.1016/j.neuropharm.2011.03.010. PMC 3139704. PMID 21459101. Retrieved 10 September 2014. Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). ...
    Table 1
     
  27. ^ Costa, VD, Lang, PJ, Sabatinelli, D, Bradley MM, and Versace, F (2010). "Emotional imagery: Assessing pleasure and arousal in the brain's reward circuitry". Human Brain Mapping 31 (9): 1446–1457. doi:10.1002/hbm.20948. PMID 20127869. 
  28. ^ Sabatinelli, D, Lang, PJ, Bradley, MM, Costa, VD, and Versace, F (2007). "Pleasure rather than salience activates human nucleus accumbens and medial prefrontal cortex". Journal of Neurophysiology 98 (9): 1374–1379. doi:10.1152/jn.00230.2007. PMID 17596422. 
  29. ^ Menon Vinod, Levitin Daniel J (2005). "The rewards of music listening: Response and physiological connectivity of themesolimbic system". NeuroImage 28 (1): 175–184. doi:10.1016/j.neuroimage.2005.05.053. 
  30. ^ Olds J, Milner P (1954). "Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain". J Comp Physiol Psychol 47 (6): 419–27. doi:10.1037/h0058775. PMID 13233369.  article
  31. ^ Nakahara D., Ozaki N., Miura Y., Miura H. et al. (1989). "Increased dopamine and serotonin metabolism in rat nucleus accumbens produced by intracranial sel-stimulation of medial forebrain bundle as measured by in vivo microdialysis". Brain Research' 495: 178–181. doi:10.1016/0006-8993(89)91234-1. 
  32. ^ Aharon L., Etcoff N., Ariely D., CHabris C. F. et al.. "Beautiful faces have variable reward value: fMRI and behavioral evidence. Neuron". 2001, 32: 357–551. 
  33. ^ Ferris C.F., Kulkarni P., Sullivan J.M., Harder J.A. et al. (2005). "Pup sucking is more rewarding than cocaine: Evidence from functional magnetic resonance imaging and three-dimensional computational analysis". Journal of Neuroscience' 25: 149–156. doi:10.1523/jneurosci.3156-04.2005. 
  34. ^ Numan M (2007). "Motivational systems and the neural circuitry of maternal behavior in the rat". Developmental Psychobiology' 49 (1): 12–21. doi:10.1002/dev.20198. PMID 17186513. 
  35. ^ a b Hyman SE, Malenka RC, Nestler EJ (2006). "Neural mechanisms of addiction: the role of reward-related learning and memory". Annu. Rev. Neurosci. 29: 565–598. doi:10.1146/annurev.neuro.29.051605.113009. PMID 16776597. 
  36. ^ Steiner H, Van Waes V (January 2013). "Addiction-related gene regulation: risks of exposure to cognitive enhancers vs. other psychostimulants". Prog. Neurobiol. 100: 60–80. doi:10.1016/j.pneurobio.2012.10.001. PMC 3525776. PMID 23085425. 
  37. ^ Kanehisa Laboratories (2 August 2013). "Alcoholism – Homo sapiens (human)". KEGG Pathway. Retrieved 10 April 2014. 
  38. ^ Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM (February 2013). "Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator". J. Neurosci. 33 (8): 3434–3442. doi:10.1523/JNEUROSCI.4881-12.2013. PMC 3865508. PMID 23426671. Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. ... Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. ... Sexual behavior is highly rewarding (Tenk et al., 2009), and sexual experience causes sensitized drug-related behaviors, including cross-sensitization to amphetamine (Amph)-induced locomotor activity (Bradley and Meisel, 2001; Pitchers et al., 2010a) and enhanced Amph reward (Pitchers et al., 2010a). Moreover, sexual experience induces neural plasticity in the NAc similar to that induced by psychostimulant exposure, including increased dendritic spine density (Meisel and Mullins, 2006; Pitchers et al., 2010a), altered glutamate receptor trafficking, and decreased synaptic strength in prefrontal cortex-responding NAc shell neurons (Pitchers et al., 2012). Finally, periods of abstinence from sexual experience were found to be critical for enhanced Amph reward, NAc spinogenesis (Pitchers et al., 2010a), and glutamate receptor trafficking (Pitchers et al., 2012). These findings suggest that natural and drug reward experiences share common mechanisms of neural plasticity 
  39. ^ Brain Electrodes Help Treat Depression, Technology Review, 26 April 2007
  40. ^ Bewernick B. H., Hurlemann R., Matusch A. et al. (2009). "Nucleus accumbens deep brain stimulation decreases ratings of depression and anciety in treatment-resistant depression". Biological Psychiatry' 67: 110–116. doi:10.1016/j.biopsych.2009.09.013. 
  41. ^ Ooms P, Mantione M, Figee M, Schuurman PR, van den Munckhof P, Denys D. Deep brain stimulation for obsessive-compulsive disorders: long-term analysis of quality of life" J Neurol Neurosurg Psychiatry 2014;85(2):153-8.
  42. ^ http://www.eurekalert.org/pub_releases/2007-07/cp-brc071607.php Brain region central to placebo effect identified

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