Lesions Of Nucleus Accumbens Research Articles

More than Addiction—The Nucleus Accumbens Contribution to Development of Mental Disorders and Neurodegenerative Diseases

Stress and negative emotions evoked by social relationships and working conditions, frequently accompanied by the consumption of addictive substances, and metabolic and/or genetic predispositions, negatively affect brain function. One of the affected structures is nucleus accumbens (NAc). Although its function is commonly known to be associated with brain reward responses and addiction, a growing body of evidence also suggests its role in some mental disorders, such as depression and schizophrenia, as well as neurodegenerative diseases, such as Alzheimer’s, Huntington’s, and Parkinson’s. This may result from disintegration of the extensive connections based on numerous neurotransmitter systems, as well as impairment of some neuroplasticity mechanisms in the NAc. The consequences of NAc lesions are both morphological and functional. They include changes in the NAc’s volume, cell number, modifications of the neuronal dendritic tree and dendritic spines, and changes in the number of synapses. Alterations in the synaptic plasticity affect the efficiency of synaptic transmission. Modification of the number and structure of the receptors affects signaling pathways, the content of neuromodulators (e.g., BDNF) and transcription factors (e.g., pCREB, DeltaFosB, NFκB), and gene expression. Interestingly, changes in the NAc often have a different character and intensity compared to the changes observed in the other parts of the basal ganglia, in particular the dorsal striatum. In this review, we highlight the role of the NAc in various pathological processes in the context of its structural and functional damage, impaired connections with the other brain areas cooperating within functional systems, and progression of the pathological processes.

Midbrain and Lateral Nucleus Accumbens Dopamine Depletion Affects Free-choice High-fat high-sugar Diet Preference in Male Rats

Dopamine influences food intake behavior. Reciprocally, food intake, especially of palatable dietary items, can modulate dopamine-related brain circuitries. Among these reciprocal impacts, it has been observed that an increased intake of dietary fat results in blunted dopamine signaling and, to compensate this lowered dopamine function, caloric intake may subsequently increase. To determine how dopamine regulates food preference we performed 6-hydroxydopamine (6-OHDA) lesions, depleting dopamine in specific brain regions in male Sprague Dawley rats. Food preference was assessed by providing the rats with free choice access to control diet, fat, 20% sucrose and tap water. Rats with midbrain lesions targeting the substantia nigra (which is also a model of Parkinson’s disease) consumed fewer calories, as reflected by a decrease in control diet intake, but they surprisingly displayed an increase in fat intake, without change in the sucrose solution intake compared to sham animals. To determine which of the midbrain dopamine projections may contribute to this effect, we next compared the impact of 6-OHDA lesions of terminal fields, targeting the dorsal striatum, the lateral nucleus accumbens and the medial nucleus accumbens. We found that 6-OHDA lesion of the lateral nucleus accumbens, but not of the dorsal striatum or the medial nucleus accumbens, led to increased fat intake. These findings indicate a role for lateral nucleus accumbens dopamine in regulating food preference, in particular the intake of fat.

Unilateral accumbal dopamine depletion affects decision-making in a side-specific manner

Mechanisms underlying affective and cognitive deficits in Parkinson's disease (PD) remain less studied than motor symptoms. Nucleus accumbens (NAc) is affected in PD and due to its well-known involvement in motivation is an interesting target in this context. Furthermore, PD is frequently asymmetrical, with side-specific deficits aligning with evidences of accumbal laterality. We therefore used a 6-hydroxydopamine (6-OHDA) model to study the role of left and right NAc dopamine depletion in a battery of behavioral tasks.2 months old male rats were used in all experiments. Habitual-based and goal-directed decision-making, impulsivity, anxiety- and depressive-like behavior and motor performance were tested 3 weeks after left (6-OHDA L) or right (6-OHDA R) NAc lesion was induced. Upon contingency degradation, 6-OHDA R decrease their lever press rate less than Sham and 6-OHDA L, indicating an impairment in the shift from habit-based to goal-directed strategies. On the other hand, 6-OHDA L lesions lead to increased rates of premature responding when delays where increased in the variable delay-to-signal test. Importantly, in both paradigms task acquisition was similar between groups. In the same line we found no differences in the amount of sugared pellets eaten when freely available as well as in both general and fine motor behaviors.In conclusion, left and right NAc play distinct roles in the contingency degradation and impulsivity. More studies are needed to understand the mechanisms behind this functional lateralization and its implications for PD patients.

Effect of ischemic lesions in medial prefrontal cortex and nucleus accumbens on affective behavior in rats

Post-stroke depression (PSD) and post-stroke anxiety (PSA) are usually undertreated and many cases may remain undiagnosed, indicating a need for a better understanding of the underlying mechanisms. Current animal models of PSD and PSA using the middle cerebral artery occlusion model may be associated with motor deficits that can interfere with behavioral tests of depression- and anxiety-like behavior. Unilateral lesions of the medial prefrontal cortex (mPFC) have been reported to induce a depression- and anxiety-like phenotype in mice. The aim of this study was to examine the effects of unilateral microinjections of the vasoconstrictor endothelin-1 (ET-1) in the mPFC alone or in combination with the nucleus accumbens (NAc) on the behavior of rats after 2 and 6 weeks. Specifically, we measured anxiety- and depressive-like behavior, locomotion, and cognition. ET-1 injections in the mPFC and NAc resulted in replicable and localized lesions. Lesions to the mPFC and NAc resulted in more time spent in the open arms of the Elevated Plus Maze compared to sham-operated animals at 2 weeks post stroke, indicating decreased anxiety. This effect did not persist until 6 weeks post injection. No differences in locomotion, cognition and depressive-like behavior were found at either time point. In summary, unilateral lesions of mPFC and NAc did not produce a reliable and persistent anxiety and depression phenotype in rats.

Seizure suppression by asynchronous non-periodic electrical stimulation of the amygdala is partially mediated by indirect desynchronization from nucleus accumbens

Electrical stimulation (ES) of the nervous system is a promising alternative for the treatment of refractory epilepsy. Based on the understanding that seizures are the expression of neural hypersynchronism, our group developed and tested a non-standard form of low-energy temporally unstructured ES termed NPS (Non-periodic stimulation), with pseudo-randomized inter-pulse intervals. Previous investigation demonstrated that NPS applied to the amygdala has a robust anticonvulsant effect against both acute and chronic seizures, and suggested that its therapeutic effect is based on direct desynchronization of ictogenic neural circuits. Further mechanistic investigation using functional magnetic resonance imaging has shown that NPS also activates nucleus accumbens (NAc) in seizure-free rats, raising the hypothesis of an alternative therapeutic mechanism: NPS-enhanced indirect inhibition / desynchronization of ictogenic circuits by NAc. In order to investigate this idea, here we evaluated behavior and cortical electrographic activity from animals submitted to pentylenetetrazole (PTZ) induced seizures, treated with NPS and with or without bilateral electrolytic lesion of NAc. NPS-treated animals with bilateral lesion of NAc expressed unexpected straub tail in addition to other stereotypical convulsive behavior, displayed increased susceptibility to PTZ (lower drug threshold), and had a much longer electrographic seizure, with a greater number of spikes, firing at a higher rate. Moreover, analysis of spike morphology showed an increase in amplitude and slope in these animals, suggesting that ablation of NAc results in disinhibition and/or increase of neural synchronism within ictogenic circuits. NPS had no therapeutic effect whatsoever in lesioned animals, while it displayed a mild anticonvulsant effect in those with intact brains. Results corroborate the notion that NAc has a key role in controlling aberrant epileptiform activity in ictogenic circuits through indirect polysynaptic connections that may enroll the ventral pallidum and ventral tegmental area. They also point to the possibility that NPS may enhance this effect, putatively by benefiting from the structure’s property of detecting saliences.

Nucleus accumbens mediates the pronociceptive effect of sleep deprivation: the role of adenosine A2A and dopamine D2 receptors.

Sleep disorders increase pain sensitivity and the risk of developing painful conditions; however, the underlying mechanisms are poorly understood. It has been suggested that nucleus accumbens (NAc) influences sleep-wake cycle by means of a balance between adenosine activity at A2A receptors and dopamine activity at D2 receptors. Because the NAc also plays an important role in pain modulation, we hypothesized that the NAc and its A2A and D2 receptors mediate the pronociceptive effect of rapid eye movement (REM) sleep deprivation (SD). We found that 24 hours of REM-SD induced an intense pronociceptive effect in Wistar rats, which decreases progressively over a sleep rebound period. Although the level of fecal glucocorticoid metabolites increased with SD within group, it did not differ between sleep-deprived group and control group, indicating a stress response with similar magnitude between groups. The pronociceptive effect of REM-SD was prevented by excitotoxic lesion (N-Methyl-D-aspartate, 5.5 μg) of NAc and reverted by its acute blockade (Qx-314, 2%). The administration of an A2A receptor antagonist (SCH-58261, 7 ng) or a D2 receptor agonist (piribedil, 6 μg) into the NAc increased home cage activity and blocked the pronociceptive effect of REM-SD. Complementarily, an A2A receptor agonist (CGS-21680, 24 ng) impaired the reversal of the pronociceptive effect and decreased home cage activity, as it did a D2 receptor antagonist (raclopride, 5 μg). Rapid eye movement SD did not affect the expression of c-Fos protein in NAc. These data suggest that SD increases pain by increasing NAc adenosinergic A2A activity and by decreasing NAc dopaminergic D2 activity.

Effect of nucleus accumbens lesions on socially motivated behaviour of young domestic chicks

Behaviour of young domestic chicks when isolated from conspecifics is influenced by two conflicting drives: fear of potential predator and craving for company. The nucleus accumbens (Ac) has been suggested to influence social behaviour, as well as motivation in goal-directed tasks. In this study, the Ac of 1-day-old domestic chicks was lesioned bilaterally, using radiofrequency method. Open field behaviour before and after presenting a silhouette of a bird of prey was recorded, followed by a behavioural test to measure group size preference and social motivation of chicks. Ac-lesioned individuals emitted more distress calls and ambulated more in the open field test, however, they reacted to the predatory stimulus very similarly to control chicks: their vocalization was reduced and the intergroup difference in motor activity also disappeared. There was no difference between the lesioned and control chicks in the latency to approach their conspecifics in the social motivation test, and both groups chose the larger flock (eight) of conspecifics over the smaller one (three). Concerning the role of Ac in social behaviour, a difference between lesioned and sham birds was evident here only in the absence of detectable stimulus (predator or conspecifics). These findings may reflect either decreased fear of exposure to predators or increased craving for conspecifics suggesting that the likely function of Ac is to modulate goal-driven, including socially driven, behaviours, especially when the direct stimulus representing the goal is absent. This is in harmony with the known promotion of impulsiveness by Ac lesions.

Dissociable contribution of nucleus accumbens and dorsolateral striatum to the acquisition of risk choice behavior in the rat

While a growing body of research has suggested that the mesocorticolimbic dopamine systems play a key role in decision making under risk, how the nucleus accumbens (NAC) is involved in the acquisition of risk choice behavior remains unclear. This study used a T-maze task to assess risk-based decision making in which the rat was required to assess the risk by choosing to enter either a small and certain reward arm or a large but uncertain reward arm of the maze. The latter option, when chosen, resulted in provision of 2, 4, or 8 sweeten pellets with a probability (p) of 0.5, 0.25, or 0.125, respectively. Thus the latter arm provided three different conditions of reward ratio, compared to the choice of former arm, which always provided 1 pellet with p=1. This risk choice task was then run with the expected value being equality between the binary choice options. The experimental rats first received an excitoneurotoxic lesion affecting either the NAC or the dorsolateral striatum (DLS) and this was followed by post-lesion behavioral examination. The sham lesion control rats acquired a stable risk choice with regard to each reward ratio over a 10-day test. The pattern of choice behavior appeared in risk-seeking when p=0.5 to obtain 2 pellets, and was risk-averse when larger reward resulted in lower p. The NAC lesion significantly disrupted the acquisition of the aforementioned risk choice behavior and apparently shifted the choice into a risk-averse style for all three reward ratios. No such effect was observed in the rats with DLS lesions. Neither the gross motor action nor the discrimination of different reward magnitudes was impaired by the lesions affecting either the NAC or DLS as assessed by an additional experiment. These findings suggest that firstly there is heterogeneity between NAC and DLS with respect to risk-based decision making, and that secondly the NAC is involved and critical to the acquisition of behavioral choice under risk, specially when the expected value of the reward under the two choice options is equal.

The effect of nucleus accumbens lesions on appetite, sexual function, and nicotine dependence in recovering heroin addicts

Abstract The nucleus accumbens (NAc) is a key part of the neural circuitry that creates reward, pleasure and motivation that facilitates human feeding, sexual and smoking behaviors. In the brain reward system, the NAc is a crucial component responsible for natural and drug-induced reinforcement behaviors. Yet it is unclear whether NAc is indispensible for all reward behaviors in human beings. The present study aimed to investigate the long-term effects of NAc ablation on sexual function, appetite, and nicotine dependence level in chronic heroin users. Eighteen former heroin-dependent patients (male) with bilateral NAc ablation via stereotactic radiofrequency surgery for alleviating drug psychological dependence were recruited. Their postoperative time ranged from 12 to 103 months. All subjects received MRI scans for assessing the accuracy of the lesion site. Evaluation of appetite, sexual function, and nicotine dependence were measured using the Simplified Nutrition Appetite Questionnaire, the Brief Sexual Function Inventory, and the Fagerström Test for Nicotine Dependence, respectively. After precluding the potential confounding variables, such as drug use (dosage and duration), post-operation duration, age, body-weight, marital status and education level, ANOVA with repeated measures revealed that the NAc ablation improved the patients’ appetite, sexual drive and sexual satisfaction. Yet there was no change in male erectile function, ejaculatory function, or nicotine dependence levels compared to the preoperative. These may suggest that although NAc is a key part of the neural circuitry, the NAc surgical lesions left the fundamental aspects of natural and drug-induced reinforcement and motivation almost intact.

Lesions of the nucleus accumbens disrupt reinforcement omission effects in rats

The reinforcement omission effects (ROEs) have been attributed to both motivational and attentional consequences of the surprising reinforcement omission. Some studies have been showed amygdala is part of a circuit involved in the ROEs modulation. The view that amygdala lesions interfere with the ROEs is supported by evidence involving amygdala in responses correlated with motivational processes. These processes depend on the operation of separate amygdala areas and their connections with other brain systems. It has been suggested the interaction between the amygdala and the nucleus accumbens (NAC) is important to the modulation of motivational processes. Recent neuroimaging studies in human revealed reward delivery enhances activity of subcortical structures (NAC and amygdala), whereas reward omission reduces the activity in these same structures. The present study aimed to clarify whether the mechanisms related to ROEs depend on NAC. Prior to acquisition training, rats received bilateral excitotoxic lesions of NAC (NAC group) or sham lesions (Sham group). Following postoperative recovery, the rats were trained on a fixed-interval with limited hold signaled schedule of reinforcement. After acquisition of stable performance, the training was changed from 100% to 50% schedule of reinforcement. Both NAC and Sham groups presented the ROEs. However, after nonreinforcement, the response rates of the NAC group were lower than those registered in the Sham group. The performance of the NAC group decreased in the period following nonreinforcement when compared to the period preceding reinforcement omission. These findings suggest the NAC is part of the neural substrate involved in the ROEs modulation.

Effects of ventral striatal lesions on first‐ and second‐order appetitive conditioning

Rats with bilateral lesions of the ventral striatal nucleus accumbens failed to acquire Pavlovian second-order conditioning to auditory stimuli paired with visual stimuli that had previously received first-order pairings with food. This deficit in second-order conditioning was specific to learning driven by incentive properties of the first-order cues, and was observed whether the first-order training had occurred prior to or after lesion surgery. Lesions also produced deficits in the display of conditioned responses to the first-order conditioned stimulus, but only when they were made after first-order training. These results suggest a specific role for the ventral striatum in acquiring and expressing incentive properties of conditioned stimuli through second-order conditioning, as well as a more general role in expressing previously acquired Pavlovian conditioned responses.

Effect of bilateral lesions of nucleus accumbens on consummatory behaviour in Wistar rats

BackgroundNucleus accumbens (NAcc) is known to be involved in reward and addictive functions. In the present study we tested parameters of ingestive activity and alcohol intake following lesions of nucleus accumbens in order to establish the role of this nucleus unequivocally. Materials and methodsMale Wistar albino rats were divided into groups, and were subjected to Sham lesion and bilateral lesion of nucleus accumbens. The consumption of water, ethanol and food were recorded daily and their body weight was noted weekly, for one week before lesion and 3 weeks following lesion. In another set, two bottle free choice test was carried out between 10% alcohol and potable water, rest of the procedures were maintained same as for the other set. ResultsThe lesioned rats showed increase in intake of alcohol (p < 0.01). There was no significant change in food intake or body weight. In two bottle free choice test, the rats consumed increased volume of fluid. There was highly increased water intake (p < 0.001). There was no significant change in their alcohol intake. The increase in water intake was significantly more than the increase seen in the alcohol intake in the group provided only alcohol. ConclusionsBilateral lesions in nucleus accumbens did not change the alcohol intake in two bottle choice test. But they showed increased water intake in two bottle choice suggesting increased thirst. The alcohol intake increases only when there is no water provided, suggesting the pivotal role of this centre in ingestive behaviour.

Long-Term Changes in the Personality and Psychopathological Profile of Opiate Addicts after Nucleus Accumbens Ablative Surgery Are Associated with Treatment Outcome

Objective: To investigate the long-term outcome and changes of the personality and psychopathological profile of opiate addicts after bilateral stereotactic nucleus accumbens (NAc) ablative surgery. Methods: 60 patients were followed up for 5 years and abstinent status and adverse events were evaluated. NAc lesion volumes and locations were obtained by postoperative MRI scans. The Chinese version of the Eysenck Personality Questionnaire (EPQ-RSC), the Symptom Checklist-90-Revised (SCL-90-R), the Beck Depression Inventory (BDI), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the World Health Organization’s Quality of Life Questionnaire – Brief Version (WHOQOL-BREF) were administered to the patients before and 5 years after the stereotactic surgery. Results: The total abstinence rate of all patients in their 5th postoperative year was 47.4%. The abstinent patients had a significantly larger lesion volume than the relapsed ones, but a larger lesion volume also increased the risk of adverse events. 5 years after surgery, the abstinent patients showed significant decreases on the Psychoticism (EPQ-P) and Neuroticism (EPQ-N) scores by EPQ-RSC, a significant decline on the Global Severity Index and the subscores in all 10 dimensions by SCL-90-R, significant decreases on the BDI and Y-BOCS scores, and significant improvements on the scores of all domains by WHOQOL-BREF, while for the relapsed patients, only the subscores of obsessive-compulsive by SCL-90-R and the Y-BOCS scores significantly decreased. Postoperative analysis revealed that the abstinent patients had a significantly better score than the relapsed ones by various instruments, and NAc lesion volumes and locations did not correlate with the outcome of any of these instruments. Conclusion: The bilateral ablation of NAc by stereotactic neurosurgery was a feasible method for alleviating psychological dependence on opiate drugs and preventing a relapse. Long-term follow-up suggested that surgery can improve the personality and psychopathological profile of opiate addicts with a trend towards normal levels, provided persistent abstinence can be maintained; relapse, on the other hand, may ruin this effect.

Associations between personality changes and nucleus accumbens ablation in opioid addicts

It has been reported that nucleus accumbens (NAc) lesions can help to prevent relapse in opioid addicts. This article aimed to investigate associations between personality changes and NAc lesions. The surgery group consisted of 78 patients who had received bilateral stereotactic lesions of the NAc to treat opioid addiction. Seventy two non-surgery opioid addicts were appropriately paired with the patients of the surgery group as the non-surgery group. All participants were interviewed in person and received urine tests, naloxone provocative tests and hair tests to determine the prevalence of relapse. Eysenck personality questionnaire (EPQ) and the health survey questionnaire (SF-36) were employed to assess personality and functional health, respectively. In the surgery group, 30 participants relapsed, and the non-relapse rate was 61.5% (48/78). Compared with the Chinese normative data, the neuroticism (N) and psychoticism (P) dimensions of the EPQ in the non-surgery group were significantly higher, whereas the lie (L) dimension was significantly lower. There was no significant difference in all dimensions of the EPQ between the surgery group and the Chinese normative data. The N dimension in the relapse group and the L dimension in the surgery group were significantly lower than those of the non-surgery group. The P dimension in the relapse group was significantly higher than that of the non-relapse group. The extraversion (E) dimension was relatively stable between these groups. Although the influence of other factors cannot be excluded, it is apparent that surgically induced NAc lesions are associated with lower P and N dimensions for opioid addicts, and a higher P dimension is associated with a tendency to relapse.

Roles of nucleus accumbens and basolateral amygdala in autoshaped lever pressing

Initially-neutral cues paired with rewards are thought to acquire motivational significance, as if the incentive motivational value of the reward is transferred to the cue. Such cues may serve as secondary reinforcers to establish new learning, modulate the performance of instrumental action (Pavlovian-instrumental transfer, PIT), and be the targets of approach and other cue-directed behaviors. Here we examined the effects of lesions of the ventral striatal nucleus accumbens (ACb) and the basolateral amygdala (BLA) on the acquisition of discriminative autoshaped lever-pressing in rats. Insertion of one lever into the experimental chamber was reinforced by sucrose delivery, but insertion of another lever was not reinforced. Although sucrose was delivered independently of the rats’ behavior, sham-lesioned rats rapidly came to press the reinforced but not the nonreinforced lever. Bilateral ACb lesions impaired the initial acquisition of sign-tracking but not its terminal levels. In contrast, BLA lesions produced substantial deficits in terminal levels of sign-tracking. Furthermore, whereas ACb lesions primarily affected the probability of lever press responses, BLA lesions mostly affected the rate of responding once it occurred. Finally, disconnection lesions that disrupted communication between ACb and BLA produced both sets of deficits. We suggest that ACb is important for initial acquisition of consummatory-like responses that incorporate hedonic aspects of the reward, while BLA serves to enhance such incentive salience once it is acquired.

Dorsal as well as ventral striatal lesions affect levels of intravenous cocaine and morphine self-administration in rats

While the ventral striatum has long been implicated in the rewarding properties of psychomotor stimulants and opiates, little attention has been paid to the possible contribution of more dorsal regions of the striatum. We have thus examined the effects of lesions in three different striatal subregions on cocaine and morphine self-administration. Different groups of rats were trained to self-administer intravenous cocaine (1.0 mg/kg/infusion) or morphine (0.5 mg/kg/infusion) first under fixed ratio (FR) and then under progressive ratio (PR) schedules of reinforcement. Upon completion of the training, independent groups received bilateral electrolytic or sham lesions of the dorsal portion of the caudate-putamen (dCPu), the ventral portion of the caudate-putamen (vCPu) or the more ventral nucleus accumbens (NAS). Following recovery, they were tested for self-administration of cocaine (0.25, 0.5, 1.0 and 1.5 mg/kg/infusion) or morphine (0.125, 0.25, 0.5 and 0.75 mg/kg/infusion) under the PR schedule. The PR responding for each drug was significantly reduced in a dose-dependent manner following lesions of dCPu, vCPu and NAS. While the relative effectiveness of these lesions is likely to be specific to the conditions of this experiment, NAS lesions reduced self-administration of each drug to a greater extent than did dCPu or vCPu lesions.

Lesions of nucleus accumbens affect morphine‐induced release of ascorbic acid and GABA but not of glutamate in rats

Our previous studies have shown that local perfusion of morphine causes an increase of extracellular ascorbic acid (AA) levels in nucleus accumbens (NAc) of freely moving rats. Lines of evidence showed that glutamatergic and GABAergic were associated with morphine-induced effects on the neurotransmission of the brain, especially on the release of AA. In the present study, the effects of morphine on the release of extracellular AA, γ-aminobutyric acid (GABA) and glutamate (Glu) in the NAc following bilateral NAc lesions induced by kainic acid (KA) were studied by using the microdialysis technique, coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD) and fluorescent detection (HPLC-FD). The results showed that local perfusion of morphine (100 µM, 1 mM) in NAc dose-dependently increased AA and GABA release, while attenuated Glu release in the NAc. Naloxone (0.4 mM) pretreated by local perfusion to the NAc, significantly blocked the effects of morphine. After NAc lesion by KA (1 µg), morphine-induced increase in AA and GABA were markedly eliminated, while decrease in Glu was not affected. The loss effect of morphine on AA and GABA release after KA lesion could be recovered by GABA agonist, musimol. These results indicate that morphine-induced AA release may be mediated at least by µ-opioid receptor. Moreover, this effect of morphine possibly depend less on the glutamatergic afferents, but more on the GABAergic circuits within this nucleus. Finally, AA release induced by local perfusion of morphine may be GABA-receptor mediated and synaptically localized in the NAc.

Nucleus accumbens lesions modulate the effects of methylphenidate

The psychostimulant methylphenidate (MPD, Ritalin) is the prescribed drug of choice for treatment of ADHD. In recent years, the diagnosis rate of ADHD has increased dramatically, as have the number of MPD prescriptions. Repeated exposure to psychostimulants produces behavioral sensitization in rats, an experimental indicator of a drug's potential liability. In studies on cocaine and amphetamine, this effect has been reported to involve the nucleus accumbens (NAc), one of the nuclei belonging to the motive circuit. The aim of this study was to investigate the role of the NAc on the expression of behavioral sensitization as a response to MPD exposure. In the present study, 20 male Sprague–Dawley rats were divided randomly into three groups: an intact control group, a sham-operated group, and a NAc bilateral electrical lesion group. Locomotor activity was assessed for the first 2 h following 2.5 mg/kg MPD injection, using open field monitoring systems. Recordings were made during 6 days of continuous MPD administration, and then upon re-challenge with the same dose following 3 days of washout. Acute MPD exposure elicited an increase in locomotor activity in all three groups. However, the NAc lesion group exhibited significantly increased locomotor activity in comparison to sham and control groups. Chronic MPD did not elicit sensitization in the NAc lesion group, while both sham and control groups did exhibit behavioral sensitization to repetitive MPD administration. These findings suggest that the NAc plays a significant role in eliciting locomotor activity as an acute effect of MPD, and in the expression of sensitization due to chronic MPD exposure.

Comparing the role of the anterior cingulate cortex and 6-hydroxydopamine nucleus accumbens lesions on operant effort-based decision making.

Both the anterior cingulate cortex (ACC) and mesolimbic dopamine, particularly in the nucleus accumbens (NAc), have been implicated in allowing an animal to overcome effort constraints to obtain greater benefits. However, their exact contribution to such decisions has, to date, never been directly compared. To investigate this issue we tested rats on an operant effort-related cost-benefit decision-making task where animals selected between two response alternatives, one of which involved investing effort by lever pressing on a high fixed-ratio (FR) schedule to gain high reward [four food pellets (HR)], whereas the other led to a small amount of food on an FR schedule entailing less energetic cost [two food pellets, low reward (LR)]. All animals initially preferred to put in work to gain the HR. Systemic administration of a D2 antagonist caused a significant switch in choices towards the LR option. Similarly, post-operatively, excitotoxic ACC lesions caused a significant bias away from HR choices compared with sham-lesioned animals. There was no slowing in the speed of lever pressing and no correlation between time to complete the FR requirement and choice performance. Unexpectedly, no such alteration in choice allocation was observed in animals following 6-hydroxydopamine NAc lesions. However, these rats were consistently slower to initiate responding when cued to commence each trial and also showed a reduction in food hoarding on a species-typical foraging task. Taken together, this implies that only ACC lesions, and not 6-hydroxydopamine NAc lesions as performed here, cause a bias away from investing effort for greater reward when choosing between competing options

Lesions of the nucleus accumbens shell can reduce activity in the elevated plus-maze

Across different behavioural tasks, nucleus accumbens (n.acc) lesions have generated conflicting effects on locomotor activity and in particular, the relative roles of the n.acc shell and core subfields in this have been controversial. To date there is only one study examining effects of lesions to the medial n.acc on elevated plus-maze (EPM) behaviour; these lesions were shown to increase both locomotor and exploratory activity. Given the well-documented distinction between shell and core, the present study sought to extend previous research by testing lesions selective to each n.acc subfield in the EPM. Results showed no statistical differences between core lesioned and sham-operated animals on any measure. In contrast, shell lesions consistently reduced locomotion and exploratory activity. This direction of effects is opposite to that previously observed after medial n.acc. lesions. In conclusion, locomotion and exploratory activity were clearly reduced by shell but not core lesions, consistent with other evidence for the functional heterogeneity of n.acc shell and core.