Striatal dopamine neurotransmission: Regulation of release and uptake

Sulzer, David; Cragg, Stephanie J.; Rice, Margaret E.

doi:10.1016/j.baga.2016.02.001

Cited by 322 publications

(359 citation statements)

References 447 publications

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“…These data are consistent with the hypothesis that tonic endogenous activation of nAChRs on striatal dopamine terminals functions to blunt the release of dopamine when those cells burst fire, and that this influence can be alleviated by decreasing (mecamylamine) or enhanced by indirectly increasing (scopolamine) activity at these receptors (Cragg, 2006;Sulzer et al, 2016;Threlfell and Cragg, 2011). To further assess this, in a subset of subjects, we examined the influence of nAChR and mAChR blockade on the NAc dopamine response to unexpected food reward presentation, a preparation known to induce robust burst firing of midbrain dopamine cells (Schultz, 2001).…”

Section: Resultssupporting

confidence: 78%

“…Activating presynaptic nAChRs on dopamine terminals with endogenous acetylcholine can trigger dopamine release (Cachope et al, 2012;Threlfell et al, 2012), but ex vivo studies have demonstrated that this modulation depends on the activity level of dopamine cells (Zhang and Sulzer, 2004;Zhang et al, 2009). Nicotinic acetylcholine receptors can facilitate low probability dopamine release, but suppress dopamine release from high-frequency stimulation (mimicking burst firing) (Exley and Cragg, 2008b;Sulzer et al, 2016;Threlfell and Cragg, 2011). Indeed, although disrupting nAChR signaling can suppress the tonic dopamine measured by microdialysis (Lim et al, 2014), the higher resolution afforded by FSCV shows that it can actually augment high-frequency phasic release under some conditions (Exley et al, 2008a;Rice and Cragg, 2004), an effect we demonstrate here in awakebehaving animals with dopamine activity generated by unexpected reward or reward cue presentation.…”

Section: Discussionmentioning

confidence: 99%

“…Modulatory mechanisms in striatal terminals can, however, regulate dopamine release. Of these, the acetylcholine receptor system has emerged as a key player (Cachope and Cheer, 2014;Cragg, 2006;Sulzer et al, 2016). Yet, little is known about the causal role of the NAc cholinergic system in motivated behavior and there is currently no evidence of acetylcholine receptor modulation of naturally-evoked and behaviorally-relevant dopamine.…”

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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Section: Resultssupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

Collins¹,

Aitken²,

Greenfield³

et al. 2016

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…One level of DA signal regulation occurs at the terminals, where expression of a variety of release-regulating heteroreceptors in the terminal membrane (Zhang and Sulzer 2012; Sulzer et al 2016) allows local environmental influence of terminal physiology and results in diverse micro-domains within terminal fields (Wightman et al 2007; Pickel 2000; Zhang et al 2015; Tritsch et al 2012). Fast-scan cyclic voltammetry (FSCV) is often used in ex vivo slice preparations to pharmacologically probe terminal receptor regulation of DA release and how terminal activity may be altered following chronic drug and alcohol administration (Ferris et al 2013; Siciliano et al 2015b; Calipari et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Chronic ethanol exposure increases inhibition of optically targeted phasic dopamine release in the nucleus accumbens core and medial shell ex vivo

Melchior

Jones

2017

Molecular and Cellular Neuroscience

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Dopamine signaling encodes reward learning and motivated behavior through modulation of synaptic signaling in the nucleus accumbens, and aberrations in these processes are thought to underlie obsessive behaviors associated with alcohol abuse. The nucleus accumbens is divided into core and shell sub-regions with overlapping but also divergent contributions to behavior. Here we optogenetically targeted dopamine projections to the accumbens allowing us to isolate stimulation of dopamine terminals ex vivo. We applied 5 pulse (phasic) light stimulations to probe intrinsic differences in dopamine release parameters across regions. Also, we exposed animals to 4 weeks of chronic intermittent ethanol vapor and measured phasic release. We found that initial release probability, uptake rate and autoreceptor inhibition were greater in the accumbens core compared to the shell, yet the shell showed greater phasic release ratios. Following chronic ethanol, uptake rates were increased in the core but not the shell, suggesting region-specific neuronal adaptations. Conversely, kappa opioid receptor function was upregulated in both regions to a similar extent, suggesting a local mechanism of kappa opioid receptor regulation that is generalized across the nucleus accumbens. These data suggest that dopamine axons in the nucleus accumbens core and shell display differences in intrinsic release parameters, and that ethanol-induced adaptations to dopamine neuron terminal fields may not be homogeneous. Also, chronic ethanol exposure induces an upregulation in kappa opioid receptor function, providing a mechanism for potential over-inhibition of accumbens dopamine signaling which may negatively impact downstream synaptic function and ultimately bias choice towards previously reinforced alcohol use behaviors.

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“…A decrease in DAT binding was also observed in sodium replete rats treated with the mineralocorticoid deoxycorticosterone acetate (DOCA) [53]. Reduction in DAT number or function would result in increased extracellular dopamine exposure time and diffusion upon release [54,55]. In turn, extracellular dopamine would be increased over longer periods of time; an effect that has been associated with generating motivation and the vigor of goal-directed behavior [56].…”

Section: Sodium Appetite As Motivated Behaviormentioning

confidence: 99%

Physiological state tunes mesolimbic signaling: Lessons from sodium appetite and inspiration from Randall R. Sakai

Fortin

Roitman

2017

Physiology & Behavior

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Sodium deficit poses a life-threatening challenge to body fluid homeostasis and generates a sodium appetite - the behavioral drive to ingest sodium. Dr. Randall R. Sakai greatly contributed to our understanding of the hormonal responses to negative sodium balance and to the central processing of these signals. Reactivity to the taste of sodium solutions and the motivation to seek and consume sodium changes dramatically with body fluid balance. Here, we review studies that collectively suggest that sodium deficit recruits the mesolimbic system to play a role in the behavioral expression of sodium appetite. The recruitment of the mesolimbic system likely contributes to intense sodium seeking and reinforces sodium consumption observed in deficient animals. Some of the hormones that are released in response to sodium deficit act directly on both dopamine and nucleus accumbens elements. Moreover, the taste of sodium in sodium deficient rats evokes a pattern of dopamine and nucleus accumbens activity that is similar to responses to rewarding stimuli. A very different pattern of activity is observed in non-deficient rats. Given the well-characterized endocrine response to sodium deficit and its central action, sodium appetite becomes an ideal model for understanding the role of mesolimbic signaling in reward, reinforcement and the generation of motivated behavior.

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Striatal dopamine neurotransmission: Regulation of release and uptake

Cited by 322 publications

References 447 publications

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

Chronic ethanol exposure increases inhibition of optically targeted phasic dopamine release in the nucleus accumbens core and medial shell ex vivo

Physiological state tunes mesolimbic signaling: Lessons from sodium appetite and inspiration from Randall R. Sakai

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