A round, but dorsally flattened structure, the NAc is located anterior to the posterior border of the anterior commissure (AC) and lies parallel to the midline. Zahm DS: Functional-anatomical implications of the nucleus accumbens core and shell subterritories. Bayer S: A correlated study of neurogenesis, morphogenesis and cytodifferentiation in the rat nucleus accumbens; in Chronister RB, De France JF (eds): The Neurobiology of the Nucleus Accumbens. J Neurosci 1983;3:189-202. Pijnenburg AJJ, van Rossum JM: Stimulation of locomotor activity following injection of dopamine into the nucleus accumbens. Volkow ND, et al: Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. Brain Res 1992;581:39-45. Bilateral ablation of the NAc has been attempted for the treatment of opiate [309,318] and alcohol [319] addiction with evidence of efficacy, although following surgery, changes in personality characteristics, short-term memory, and attention have been noted [308]. Rauch SL, et al: A functional neuroimaging investigation of deep brain stimulation in patients with obsessive-compulsive disorder. Muschamp JW, Nemeth CL, Robison AJ, Nestler EJ, Carlezon WA Jr: FosB enhances the rewarding effects of cocaine while reducing the pro-depressive effects of the kappa-opioid receptor agonist U50488. Brain Res 1997;757:280-284. CREB-mediated transcription in the VTA-NAc pathway may be partly responsible for changes in mood, with studies suggesting that elevations of CREB within the NAc produce anhedonia, lowered affect, and decrease the rewarding effects of drugs of abuse [298,299,300]. J Comp Neurol 1987;258:317-338. J Neurosurg 2004;101:682-686. Corrigall W, Franklin K, Coen K, Clarke P: The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Hamilton MH, De Belleroche JS, Gardiner IM, Herberg LJ: Stimulatory effect of. On a molecular level, studies have noted core-shell differences in the distribution of a number of neuroactive substances and receptors, including substance P [39], calretinin [39], DA [66], serotonin [66], and serotonin receptors [67], with a tendency for these substances to be preferentially located in the shell than the core. Mavridis I, Boviatsis E, Anagnostopoulou S: Stereotactic anatomy of the human nucleus accumbens: from applied mathematics to microsurgical accuracy. Graybiel AM: Correspondence between the dopamine islands and striosomes of the mammalian striatum.
Long-term follow-up notes continued effectiveness [318], but a lack of extensive long-term data has halted the use of ablative treatments, especially in light of the ethical concerns of intentionally causing irreversible damage to brain structures with as many cognitive and behavioral functions as the NAc. This difference in development has led to the suggestion that the activation of the subcortical system is disproportionately weighted during development, which may lead to a focus on immediate over long-term gains during adolescence [30]. Carr GD, White NM: Conditioned place preference from intra-accumbens but not intra-caudate amphetamine injections. Behav Brain Res 1997;89:107-113. Here, we review the existing literature regarding several areas critical to the development of new therapies, including the known pharmacology, physiology, and connectivity of the NAc, as well as evidence supporting the potential for various NAc surgical therapies in animal models. Wiltgen BJ, Law M, Ostlund S, Mayford M, Balleine BW: The influence of Pavlovian cues on instrumental performance is mediated by CaMKII activity in the striatum. Carlezon WA Jr, Wise RA: Rewarding actions of phencyclidine and related drugs in nucleus accumbens shell and frontal cortex. Prog Neurobiol 1998;54:679-720. However, studies from the latter half of the century found reason to challenge this terminology. Carlezon WA Jr, Wise RA: Microinjections of phencyclidine (PCP) and related drugs into nucleus accumbens shell potentiate medial forebrain bundle brain stimulation reward. Dani JA, Heinemann S: Molecular and cellular aspects of nicotine abuse. Psychopharmacology (Berl) 2011;213:337-354. Caboche J, Vernier P, Rogard M, Besson MJ: Haloperidol increases PPE mRNA levels in the caudal part of the nucleus accumbens in the rat. Your Brain, Explained is a personal tour around your gray matter. Stereotact Funct Neurosurg 2003;81:96-104. Clinical applications to date of focal surgical interventions into the NAc have been intriguing but likely represent only the beginning of what may become a very important area of clinical exploration for stereotactic neurosurgeons. Neuroscience 1997;77:141-153. Alexander GE, Crutcher MD, DeLong MR: Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, prefrontal' and limbic' functions. Heimer L: Basal forebrain in the context of schizophrenia. Neurogenesis of its neurons. Physiol Behav 2002;76:379-387. J Neurophysiol 1985;54:1553-1567. Hernandez PJ, Sadeghian K, Kelley AE: Early consolidation of instrumental learning requires protein synthesis in the nucleus accumbens. Donzanti BA, Uretsky NJ: Effects of excitatory amino acids on locomotor activity after bilateral microinjection into the rat nucleus accumbens: possible dependence on dopaminergic mechanisms. Neuroscience 2005;134:737-744. Animal models of addiction have also demonstrated the importance of accumbal glutamate in response reinforcement learning [210], which may play a role in nicotine reward [211], and dissociable differences in drug-seeking behavior mediated by core and shell glutamate neurons [212]. The NAc is a complex and fascinating structure that has great influence over a variety of human behaviors. J Pharm Pharmacol 1973;25:1003-1005. Science 1989;246:385-388. Brain Res 1995;675:325-328. Behav Brain Res 1994;65:181-193.
Kumar R, et al: Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). Psychopharmacology (Berl) 2007;191:521-550. Pharmacol Biochem Behav 1989;34:899-904. Patel S, Roberts J, Moorman J, Reavill C: Localization of serotonin-4 receptors in the striatonigral pathway in rat brain. Neuroscience 1992;50:751-767. Neuroscience 2006;139:813-820. There appear to be two main cholinergic pathways that influence the reward pathways: (1) a forebrain projection from the nucleus basalis magnocellularis to the basolateral amygdala [213] that has been linked to drug relapse [214] and (2) a hindbrain projection from the mesopontine cell groups [213] (specifically the pedunculopontine tegmental nucleus (Ch5) and laterodorsal tegmental nucleus (Ch6) [215]) to the VTA and substantia nigra that modulates accumbal DA neurons [216,217] and has been linked to psychosis and schizophrenia [218]. Science 2006;311:77-80. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. J Neuropsychiatry Clin Neurosci 1999;11:71-78. Gao G, et al: Clinical study for alleviating opiate drug psychological dependence by a method of ablating the nucleus accumbens with stereotactic surgery. As such, focal modulation of the biology of the NAc with deep brain stimulation or novel biological therapies such as gene therapy or cell transplantation could have a major impact upon disorders such as depression and drug addiction. 525 East 68th Street, New York, NY 10028 (USA), Keywords: Nucleus accumbensVentral striatumDepressionAddictionObsessive-compulsive disorderPsychosurgery. Mcdonald AJ: Organization of amygdaloid projections to the prefrontal cortex and associated striatum in the rat. Heldmann M, et al: Deep brain stimulation of nucleus accumbens region in alcoholism affects reward processing. Marcus MM, Nomikos GG, Svensson TH: Differential actions of typical and atypical antipsychotic drugs on dopamine release in the core and shell of the nucleus accumbens. Koob GF, Maldonado R, Stinus L: Neural substrates of opiate withdrawal. The NAc first became a structure of interest among behavioral neuroscientists with the discovery that DA [179,180] and DA agonist injections [181] into the NAc enhanced locomotor activity in rats, suggesting that a motor stimulant is partly mediated by D1 receptors. Biol Psychiatry 1990;28:297-307. Johnston eventually recanted and once again called the area the nucleus accumbens septi', but still emphasized that this area must be recognized as an olfactory center separate from the rest of the striatum [6]. Sci Transl Med 2010;2:54ra76. Pharmacopsychiatry 2009;42:288-291. Front Behav Neurosci 2012;6:31. Neuroscientists are still trying to understand the exact role of the nucleus accumbens in these associative learning processes. Behav Brain Res 2009;199:89-102. King D, Zigmond MJ, Finlay JM: Effects of dopamine depletion in the medial prefrontal cortex on the stress-induced increase in extracellular dopamine in the nucleus accumbens core and shell. While both the core and shell project to the entopeduncular nucleus (the rodent equivalent of the human globus pallidus internus), only the shell appears to project diffusely throughout the rostrocaudal extent of the lateral hypothalamus and to the extended amygdala [19,115]. Neuroscience 1999;93:1349-1358. PREV
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Synapse 1996;23:224-231. Surg Radiol Anat 2011;33:405-414. The trajectory in most cases passes through the anterior limb of the internal capsule, entering just anterior to the coronal suture and slightly lateral to the mid-pupillary line (fig. Neuropharmacology 1981;20:29-37. Given the known connections outlined above, it is not surprising that a recent large animal study supported the influence of NAc DBS on a variety of brain structures which could influence these and other psychiatric disorders [333]. J Comp Neurol 1993;338:255-278. 2). J Neurosci 2006;26:6583-6588. Furthermore, studies have demonstrated that a number of substances can influence the accumbens, including cocaine [227,228,229,230,231], opiates [232] (for review, see [233,234]), ethanol [235], nicotine [236,237], THC [238], heroin [238], and PCP [239,240]. DA turnover is higher in the accumbens than the rest of the striatum, but not significantly different between the core and shell [66]. Technique for autoradiographic localization of the binding of [. Neuner I, et al: From psychosurgery to neuromodulation: deep brain stimulation for intractable Tourette syndrome. Br J Pharmacol 1979;67:430P-431P. Grant S, et al: Activation of memory circuits during cue-elicited cocaine craving. Neurosci Biobehav Rev 2002;26:321-352. Zabek M, Sobstyl M, Koziara H, Dzierzecki S: Deep brain stimulation of the right nucleus accumbens in a patient with Tourette syndrome. Brain Res 1977;130:217-227. Eur J Neurosci 1994;6:1255-1264. Interestingly, addictive behavior may persist even after subsequent lesions of DA neurons [264,265] suggesting the involvement of other neurotransmitter systems in learned behavior and reward. Kelley AE, Smith-Roe SL, Holahan MR: Response-reinforcement learning is dependent on. Minamino N, Masuda H, Kangawa K, Matsuo H: Regional distribution of neuromedin K and neuromedin L in rat brain and spinal cord. Neuroscience 1987;23:103-120. Similar to other striatal tissue, many of the efferent fibers terminate in the diencephalon or the pallidal complex, with projections reaching the stria terminalis, preoptic region, nucleus parataenialis, nucleus mediodorsalis thalami, lateral habenular nucleus, substantia nigra-ventral tegmental area, the lateral hypothalamus, cingulum, thalamus, globus pallidus, and subpallidal region [9,17,75,105,106,107,108,109]. Follow the instructions and try to log in again. Synapse 1996;24:308-311. This inconsistency highlights the need for a uniform surgical procedure to produce comparable results. However, it has been noted that this discrepancy may be due to technical difficulties isolating the NAc with current technology [260,263]. Wadenberg M-L, Ericson E, Magnusson O, Ahlenius S: Suppression of conditioned avoidance behavior by the local application of ()sulpiride into the ventral, but not the dorsal, striatum of the rat. The patches project to the substantia nigra pars compacta, while the matrix projects to the substantia nigra pars reticulata. Neuromodulation 2008;11:13-22. These include gradients of rostrocaudal differentiation in terms both of structure and function of the NAc [44,45,46,47] as well as organizational structures based upon differences in immunostaining and signaling molecules in the ventral and medial areas [48,49]. The success of DBS in improving motor function in dystonia, essential tremor, and Parkinson's disease [320,321], with better stability and fewer adverse effects compared with lesioning, has opened the door for trials evaluating its efficacy in treating a host of neurologic and psychiatric disorders. 
