The nucleus accumbens and learning and memory

Setlow, Barry

doi:10.1002/(sici)1097-4547(19970901)49:5<515::aid-jnr1>3.3.co;2-h

Cited by 30 publications

(36 citation statements)

References 40 publications

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“…Much previous evidence has implicated the NAc in appetitive Pavlovian and instrumental learning (1,2,31) in ways that are readily distinguishable from its well known involvement in motivation, reinforcement, and motor activity (32). In particular, the NAc has been implicated in the acquisition and͞or consolidation of spatial information but not in its retrieval (1,33).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the NAc has been implicated in the acquisition and͞or consolidation of spatial information but not in its retrieval (1,33). In intact rats, place learning in the aversively motivated Morris water maze is impaired by pretraining intra-NAc infusions of haloperidol (34) and by posttraining intra-NAc infusions of sulpiride (3) and AP-5 (7), but not by posttraining intra-NAc infusions of the AMPA receptor antagonist DNQX (7).…”

Section: Discussionmentioning

confidence: 99%

“…consolidation ͉ dopamine ͉ learning ͉ autoshaping ͉ glutamate T he nucleus accumbens (NAc) is increasingly regarded as a key forebrain structure underlying appetitive learning and memory (1,2), and there is widespread interest in understanding the involvement of NAc dopamine (DA) and glutamate in this process (3)(4)(5)(6)(7). Blockade of D1 and NMDA receptors in the NAc impairs the acquisition, but not the performance, of appetitive instrumental conditioning (4,8).…”

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Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens

Dalley

Lääne

Theobald

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

199

147

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Recent research has implicated the nucleus accumbens (NAc) in consolidating recently acquired goal-directed appetitive memories, including spatial learning and other instrumental processes. However, an important but unresolved issue is whether this forebrain structure also contributes to the consolidation of fundamental forms of appetitive learning acquired by Pavlovian associative processes. In addition, although dopaminergic and glutamatergic influences in the NAc have been implicated in instrumental learning, it is unclear whether similar mechanisms operate during Pavlovian conditioning. To evaluate these issues, the effects of posttraining intra-NAc infusions of D1, D2, and NMDA receptor antagonists, as well as D-amphetamine, were determined on Pavlovian autoshaping in rats, which assesses learning by discriminated approach behavior to a visual conditioned stimulus predictive of food reward. Intracerebral infusions were given either immediately after each conditioning session to disrupt early memory consolidation or after a delay of 24 h. Findings indicate that immediate, but not delayed, infusions of both D1 (SCH 23390) and NMDA (AP-5) receptor antagonists significantly impair learning on this task. By contrast, amphetamine and the D2 receptor antagonist sulpiride were without significant effect. These findings provide the most direct demonstration to date that D1 and NMDA receptors in the NAc contribute to, and are necessary for, the early consolidation of appetitive Pavlovian learning.consolidation ͉ dopamine ͉ learning ͉ autoshaping ͉ glutamate T he nucleus accumbens (NAc) is increasingly regarded as a key forebrain structure underlying appetitive learning and memory (1, 2), and there is widespread interest in understanding the involvement of NAc dopamine (DA) and glutamate in this process (3-7). Blockade of D1 and NMDA receptors in the NAc impairs the acquisition, but not the performance, of appetitive instrumental conditioning (4,8). Likewise, antagonism of NAc NMDA and DA receptors (9), as well as selective NAc DA depletion (10, 11), impairs Pavlovian conditioned behavior. However, because all of these studies manipulated NAc DA and glutamate function prior to conditioning, it is possible that several processes relevant to learning and memory were affected, including acquisition, consolidation, and retrieval. Posttraining manipulations define more precisely the nature of the learning deficit, in addition to avoiding possible confounding effects of nonspecific performance factors on learning (12). Indeed, a number of studies report significant effects on radial maze and water maze learning after posttraining systemic (13,14), intracaudate (15), and intra-NAc (3) administration of DA receptor agents. Furthermore, recent research indicates that early consolidation of instrumental learning requires new protein synthesis in the NAc (16).However, there have been remarkably few studies investigating the involvement of DA and glutamate in the consolidation of appetitive Pavlovian learning. Although posttraini...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens

Dalley

Lääne

Theobald

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

199

147

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“…We suspect, however, that it is relatively unlikely that intra-NAc infusions of LY379268 selectively interfered with memory retrieval. In a review of the literature on the role of the NAc in learning and memory, Setlow (1997) concluded that 'ythe NAc is involved in learning and/or consolidation, but not in retrieval, suggesting that the NAc is a permanent site of memory storage' (p 517). For example, Sutherland and Rodriguez (1989) found that prior to training, lesions of the NAc impaired learning in a spatial version of the Morris water-maze task; however, when lesions were performed post-training, they had no effect on task performance, see also Ploeger et al (1994), but see Seamans and Phillips (1994) for different results in a study using a radial arm-maze task.…”

Section: Psychological Mechanisms Underlying the Effect Of Ly379268 Nmentioning

confidence: 99%

Activation of Group II Metabotropic Glutamate Receptors in the Nucleus Accumbens Shell Attenuates Context-Induced Relapse to Heroin Seeking

Bossert

Gray

Lü

et al. 2005

Neuropsychopharmacol

216

173

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Using a rat relapse model, we previously reported that re-exposing rats to a drug-associated context, following extinction of operant responding in a different context, reinstates heroin seeking. In an initial pharmacological characterization, we found that the mGluR 2/3 agonist LY379268, which acts centrally to reduce evoked glutamate release, attenuates context-induced reinstatement of heroin seeking when injected systemically or into the ventral tegmental area, the cell body region of the mesolimbic dopamine system. Here, we tested whether injections of LY379268 into the nucleus accumbens (NAc), a terminal region of the mesolimbic dopamine system, would also attenuate context-induced reinstatement of heroin seeking. Rats were trained to self-administer heroin; drug infusions were paired with a discrete tone-light cue. Subsequently, lever pressing was extinguished in the presence of the discrete cue in a context that differed from the drug self-administration context in terms of visual, auditory, tactile, and circadian cues. After extinction of responding, LY379268 was injected to different groups of rats into the NAc core or shell or into the caudate-putamen, a terminal region of the nigrastriatal dopamine system. Injections of LY379268 into the NAc shell (0.3 or 1.0 mg) dose-dependently attenuated context-induced reinstatement of heroin seeking. Injections of 1.0 mg of LY379268 into the NAc core had no effect, while a higher dose (3.0 mg) decreased this reinstatement. Injections of LY379268 (3.0 mg) 1.5 mm dorsal from the NAc core into the caudate-putamen were ineffective. Results suggest an important role of glutamate transmission in the NAc shell in context-induced reinstatement of heroin seeking.

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“…The nucleus accumbens (NAc) and its associated circuitry have been linked to the acquisition of adaptive motor responses and the control of behaviors related to natural reinforcers (Setlow 1997;Parkinson et al 2000;Corbit et al 2001). Because of the rich glutamatergic and dopaminergic innervation of the NAc from regions associated with motivational, cognitive, and sensory processes, many studies have focused on the role of these neurotransmitter systems with respect to instrumental and incentive learning (Berridge and Robinson 1998;Cardinal et al 2002;Beninger and Gerdjikov 2004;Kelley 2004).…”

mentioning

confidence: 99%

AMPA/kainate, NMDA, and dopamine D1 receptor function in the nucleus accumbens core: A context-limited role in the encoding and consolidation of instrumental memory

Hernandez¹,

Andrzejewski²,

Sadeghian³

et al. 2005

Learn. Mem.

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Neural integration of glutamate-and dopamine-coded signals within the nucleus accumbens (NAc) is a fundamental process governing cellular plasticity underlying reward-related learning. Intra-NAc core blockade of NMDA or D1 receptors in rats impairs instrumental learning (lever-pressing for sugar pellets), but it is not known during which phase of learning (acquisition or consolidation) these receptors are recruited, nor is it known what role AMPA/kainate receptors have in these processes. Here we show that pre-trial intra-NAc core administration of the NMDA, AMPA/KA, and D1 receptor antagonists AP-5 (1 µg/0.5 µL), LY293558 (0.01 or 0.1 µg/0.5 µL), and SCH23390 (1 µg/0.5 µL), respectively, impaired acquisition of a lever-pressing response, whereas post-trial administration left memory consolidation unaffected. An analysis of the microstructure of behavior while rats were under the influence of these drugs revealed that glutamatergic and dopaminergic signals contribute differentially to critical aspects of the initial, randomly emitted behaviors that enable reinforcement learning. Thus, glutamate and dopamine receptors are activated in a time-limited fashion-only being required while the animals are actively engaged in the learning context.In order to survive in changing environments, animals must be able to acquire, consolidate, and retrieve pertinent information regarding a given stimulus situation. The ability to learn associations between various stimuli and events, including motor actions, is the basis of instrumental learning (Rescorla 1991;Dickinson and Balleine 1994). Appetitive instrumental learning occurs when an animal associates its behavior with a favorable outcome such as food, sex, or the avoidance of pain. For instance, in a common experimental model of instrumental learning, a hungry rat learns to press a lever to obtain a food reward.The nucleus accumbens (NAc) and its associated circuitry have been linked to the acquisition of adaptive motor responses and the control of behaviors related to natural reinforcers (Setlow 1997;Parkinson et al. 2000;Corbit et al. 2001). Because of the rich glutamatergic and dopaminergic innervation of the NAc from regions associated with motivational, cognitive, and sensory processes, many studies have focused on the role of these neurotransmitter systems with respect to instrumental and incentive learning (Berridge and Robinson 1998;Cardinal et al. 2002;Beninger and Gerdjikov 2004;Kelley 2004). For example, blockade of glutamate (N-methyl-D-aspartate, NMDA) or dopamine D1 receptors within the NAc core potently impairs instrumental learning, and coinfusion of low, individually ineffective doses of AP-5 and SCH23390 also prevents learning, suggesting that convergence of both systems on post-synaptic neurons is required In the aforementioned studies, pre-trial blockade of NMDA and D1 receptors appeared to prevent the encoding (or acquisition) of information; however, it is possible that disruption of the consolidation phase of learning or retrieval could have contribut...

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The nucleus accumbens and learning and memory

Cited by 30 publications

References 40 publications

Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens

Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens

Activation of Group II Metabotropic Glutamate Receptors in the Nucleus Accumbens Shell Attenuates Context-Induced Relapse to Heroin Seeking

AMPA/kainate, NMDA, and dopamine D1 receptor function in the nucleus accumbens core: A context-limited role in the encoding and consolidation of instrumental memory

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