Nucleus Accumbens Acetylcholine Regulates Appetitive Learning and Motivation for Food via Activation of Muscarinic Receptors.

Pratt, Wayne E.; Kelley, Ann E.

doi:10.1037/0735-7044.118.4.730

Cited by 85 publications

(87 citation statements)

References 52 publications

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“…In FR models, animals increase their rate of self-administration as the unit dose of a drug is decreased (to compensate for decreases in the unit dose) and reduce responding as the unit dose is increased (Arnold and Roberts, 1997;Koob, 2000). Progressive ratio schedules are used to evaluate the reinforcing efficacy of a selfadministered drug by increasing the response requirements for each successive reinforcement and determining the (Ikemoto and Wise, 2002;Redgrave and Horrell, 1976) Rewarding effect of cocaine mediated through M 5 receptors (Fink-Jensen et al, 2003;Thomsen et al, 2005;Yeomans and Baptista, 1997;Yeomans et al, 2001) Striatum Striatal ACh increase associated with reward, possibly satiation (Imperato et al, 1993a, b;Mark et al, 1992;Pratt and Kelley, 2004;Zocchi and Pert, 1994).…”

Section: Overview Of Animal Models Of Addictionmentioning

confidence: 99%

“…Unlike the relatively quick increase in ACh observed by Mark et al (1992), reported a maximal ACh after the sucrose meal ended. The involvement of NAc ACh in food reward appears to be mediated by mAChR, as the administration of scopolamine (1.0 or 10.0 mg/side) into the NAc core or shell inhibited both the appetitive learning and the number of lever presses expended for the sucrose, whereas mecamylamine (10.0 mg/side) did not (Pratt and Kelley, 2004). In a follow-up study, Pratt and Kelley (2005) reported that both ventrally and dorsally administered scopolamine into the striatum (0.5 or 10.0 mg/bilaterally) reduced 24-h food intake without affecting water intake.…”

Section: Striatal Acetylcholine and Rewardmentioning

confidence: 99%

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The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

160

138

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Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.

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Section: Overview Of Animal Models Of Addictionmentioning

confidence: 99%

Section: Striatal Acetylcholine and Rewardmentioning

confidence: 99%

The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

160

138

View full text Add to dashboard Cite

show abstract

“…Coordinates were selected based on the previous findings demonstrating effects of cholinergic receptor antagonists on reward-related behavior (Nadal et al, 1998;Pratt and Kelley, 2004) and to avoid spread into the NAc shell. For Experiment 2, calibrated carbon-fiber microelectrodes coupled with guide cannulae were implanted unilaterally into the NAc (AP: +1.3 mm; ML: ± 1.3; V: − 7.0 from dura) along with an Ag/AgCl reference electrode in the contralateral cortex.…”

Section: Surgical Proceduresmentioning

confidence: 99%

“…All rats were tested under each drug condition, counterbalanced for order. Doses were selected based on their ability to alter reward seeking when infused into the NAc, without causing gross motor impairments (Nadal et al, 1998;Nunes et al, 2013;Pratt and Kelley, 2004). Drugs were infused, as described previously (Wassum et al, 2009), into the NAc in a volume of 0.5 μl over 1 min via an injector inserted into the guide cannula fabricated to protrude 1 mm ventral to the cannula tip, using a microinfusion pump.…”

Section: Drugs and Infusion Proceduresmentioning

confidence: 99%

“…NAc mAChRs have been implicated in instrumental activity (Ikemoto et al, 1998;Pratt and Kelley, 2004), but neither their precise contribution, nor involvement in cue-motivated behavior has been determined. Therefore, here we tested the hypothesis that NAc endogenous mAChR and nAChR activity regulates expression of the motivational value of reward-predictive cues and then examined a potential dopaminergic mechanism for this influence.…”

Section: Introductionmentioning

confidence: 99%

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Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

Collins¹,

Aitken²,

Greenfield³

et al. 2016

Neuropsychopharmacol

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Environmental reward-predictive cues can motivate reward-seeking behaviors. Although this influence is normally adaptive, it can become maladaptive in disordered states, such as addiction. Dopamine release in the nucleus accumbens core (NAc) is known to mediate the motivational impact of reward-predictive cues, but little is known about how other neuromodulatory systems contribute to cue-motivated behavior. Here, we examined the role of the NAc cholinergic receptor system in cue-motivated behavior using a Pavlovian-to-instrumental transfer task designed to assess the motivating influence of a reward-predictive cue over an independently-trained instrumental action. Disruption of NAc muscarinic acetylcholine receptor activity attenuated, whereas blockade of nicotinic receptors augmented cue-induced invigoration of reward seeking. We next examined a potential dopaminergic mechanism for this behavioral effect by combining fast-scan cyclic voltammetry with local pharmacological acetylcholine receptor manipulation. The data show evidence of opposing modulation of cue-evoked dopamine release, with muscarinic and nicotinic receptor antagonists causing suppression and augmentation, respectively, consistent with the behavioral effects of these manipulations. In addition to demonstrating cholinergic modulation of naturally-evoked and behaviorally-relevant dopamine signaling, these data suggest that NAc cholinergic receptors may gate the expression of cue-motivated behavior through modulation of phasic dopamine release.

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A proposed hypothalamic–thalamic–striatal axis for the integration of energy balance, arousal, and food reward

Kelley

Baldo

Pratt

2005

J of Comparative Neurology

Self Cite

311

286

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We elaborate herein a novel theory of basal ganglia function that accounts for why palatable, energy-dense foods retain high incentive value even when immediate physiological energy requirements have been met. Basal ganglia function has been studied from the perspective of topographical segregation of processing within parallel circuits, with primary focus on motor control and cognition. Recent findings suggest, however, that the striatum can act as an integrated unit to modulate motivational state. We describe evidence that the striatal enkephalin system, which regulates the hedonic impact of preferred foods, undergoes coordinated gene expression changes that track current motivational state with regard to food intake. Striatal enkephalin gene expression is also downregulated by an intrastriatal infusion of a cholinergic muscarinic antagonist, a manipulation that greatly suppresses food intake. To account for these findings, we propose that signaling through a hypothalamic-midline thalamic-striatal axis impinges on the cholinergic interneurons of the striatum, which via their large, overlapping axonal fields act as a network to modulate enkephalin-containing striatal output neurons. A key relay in this circuit is the paraventricular thalamic nucleus, which receives convergent input from orexin-coded hypothalamic energy-sensing and behavioral state-regulating neurons, as well as from circadian oscillators, and projects to cholinergic interneurons throughout the striatal complex. We hypothesize that this system evolved to coordinate feeding and arousal, and to prolong the feeding central motivational state beyond the fulfillment of acute energy needs, thereby promoting "overeating" and the consequent development of an energy reserve for potential future food shortages.

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Nucleus Accumbens Acetylcholine Regulates Appetitive Learning and Motivation for Food via Activation of Muscarinic Receptors.

Cited by 85 publications

References 52 publications

The Role of Acetylcholine in Cocaine Addiction

The Role of Acetylcholine in Cocaine Addiction

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

A proposed hypothalamic–thalamic–striatal axis for the integration of energy balance, arousal, and food reward

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