One month of cocaine abstinence potentiates rapid dopamine signaling in the nucleus accumbens core

Cameron, Courtney M.; Wightman, R. Mark; Carelli, Regina M.

doi:10.1016/j.neuropharm.2016.09.006

Cited by 16 publications

(15 citation statements)

References 51 publications

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“…; Cameron et al . ), heightened extinction responding in our 30‐day abstinent group was not observed here, even in high aversive rats. This finding is likely related to specifics of our task and the severe dysphoric state elicited by it.…”

Section: Discussionsupporting

confidence: 48%

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Drug‐induced dysphoria is enhanced following prolonged cocaine abstinence and dynamically tracked by nucleus accumbens neurons

et al. 2018

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Negative reinforcement models postulate that addicts use drugs to alleviate negative affective states (e.g. dysphoria) associated with withdrawal. In a pre-clinical model, rats exhibit negative affect to a normally rewarding tastant when it predicts impending, but delayed cocaine, and nucleus accumbens (NAc) neurons dynamically track this state. Here, we examined the effects of short versus prolonged experimenter-imposed cocaine abstinence on negative affect, cocaine seeking and self-administration. Rats were given 14 saccharin-cocaine sessions; NAc activity and affective responses to the taste (i.e. taste reactivity) were measured during sessions 1 and 14. Next, following 1 or 30 days of abstinence, taste reactivity and cell firing were recorded in a three-phase test session: (1) intraoral saccharin infusions, (2) extinction and (3) cocaine self-administration. Results showed that 30 days of abstinence led to a significant enhancement of aversive responses to the cocaine-paired tastant, accompanied by a dramatic decline in NAc phasic activity during tastant infusion. While extinction behavior did not differ across groups, NAc phasic firing reemerged during drug seeking. Further, when drug was again readily available, greater aversion to the drug-paired tastant before and after abstinence was associated with increased self-administration following prolonged (30-day) abstinence in rats classified as high (not low) aversive. Collectively, these findings show that drug-induced dysphoria is enhanced following prolonged cocaine abstinence and that NAc neural signaling is dynamic, dampening when negative affect is at its highest (phase 1), but transitioning back 'online' during subsequent drug seeking and taking (phases 2 and 3).

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Section: Discussionsupporting

confidence: 48%

“…; Hollander & Carelli , ; Pickens et al . ; Cameron, Wightman & Carelli ; Wolf ). Further, anhedonia such as that experienced during drug withdrawal is associated with weak ventral striatal activity in humans (Der‐Avakian & Markou ).…”

Section: Introductionmentioning

confidence: 99%

Drug‐induced dysphoria is enhanced following prolonged cocaine abstinence and dynamically tracked by nucleus accumbens neurons

et al. 2018

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“…The k activation alone inhibits evoked dopamine in the NAc, and, on a short time scale, pretreatment with a k agonist attenuates the dopamine response to cocaine in the NAc (Ehrich et al, 2014). However, on a longer time scale, pretreatment with a k agonist increases the cocaine-induced increase in NAc dopamine (Ehrich et al, 2014), similar to potentiated dopamine release after .24-hour withdrawal, or 30 days of forced abstinence (Addy et al, 2010;Cameron et al, 2016). Further work is needed to determine whether k opioid receptor activation alone can explain the differences between these studies (Addy et al, 2010;Siciliano et al, 2015b;Cameron et al, 2016).…”

Section: Adaptations In Catecholamine Functionmentioning

confidence: 99%

“…However, on a longer time scale, pretreatment with a k agonist increases the cocaine-induced increase in NAc dopamine (Ehrich et al, 2014), similar to potentiated dopamine release after .24-hour withdrawal, or 30 days of forced abstinence (Addy et al, 2010;Cameron et al, 2016). Further work is needed to determine whether k opioid receptor activation alone can explain the differences between these studies (Addy et al, 2010;Siciliano et al, 2015b;Cameron et al, 2016). Regardless, the timecourse dependence of k opioid modulation of dopamine is interesting in the context of stress-induced cocaine use.…”

Section: Adaptations In Catecholamine Functionmentioning

confidence: 99%

Contrasting Regulation of Catecholamine Neurotransmission in the Behaving Brain: Pharmacological Insights from an Electrochemical Perspective

Fox

Wightman

2016

Pharmacol Rev

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Catecholamine neurotransmission plays a key role in regulating a variety of behavioral and physiologic processes, and its dysregulation is implicated in both neurodegenerative and neuropsychiatric disorders. Over the last four decades, in vivo electrochemistry has enabled the discovery of contrasting catecholamine regulation in the brain. These rapid and spatially resolved measurements have been conducted in brain slices, and in anesthetized and freely behaving animals. In this review, we describe the methods enabling in vivo measurements of dopamine and norepinephrine, and subsequent findings regarding their release and regulation in intact animals. We thereafter discuss key studies in awake animals, demonstrating that these catecholamines are not only differentially regulated, but are released in opposition of each other during appetitive and aversive stimuli.

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“…In those studies, however, DA kinetics were often examined in ex vivo brain slice preparations (e.g., Ferris et al, 2013), which may differ from how these systems may operate in awake and behaving animals. Further, although some of these experiments have examined how cocaine exerts long-term effects after prolonged drug abstinence (Cameron et al, 2016; Siciliano et al, 2016), none have investigated whether the extended withdrawal from drug taking differentially affects DA signaling in core and shell.…”

Section: Introductionmentioning

confidence: 99%

Terminal Dopamine Release Kinetics in the Accumbens Core and Shell Are Distinctly Altered after Withdrawal from Cocaine Self-Administration

Saddoris

2016

eNeuro

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Repeated self-administration of cocaine is associated with impairments in motivated behaviors as well as alterations in both dopamine (DA) release and neural signaling within the nucleus accumbens (NAc). These impairments are present even after several weeks of abstinence from drug taking, suggesting that the self-administration experience induces long-lasting neuroplastic alterations in the mesolimbic DA circuit. To understand these changes at the terminal level, rats were allowed to self-administer either cocaine intravenously (∼1 mg/kg per infusion) or water to a receptacle (control) in 2-h sessions over 14 days, followed by 30 days of enforced abstinence. Fast-scan cyclic voltammetry was used to record real-time DA release in either NAc core or shell after electrical stimulations of the ventral tegmental area (VTA) in freely-moving animals. In controls, the kinetics of DA release in the core and shell strikingly differed, with shell displaying slower release and reuptake rates than core. However, cocaine experience differentially altered these signaling patterns by NAc subregion. In the shell, cocaine rats showed less sensitivity to the dynamic range of applied stimulations than controls. In the core, by contrast, cocaine rats displayed robustly reduced peak DA release given the same stimulation, while also showing slower release and reuptake kinetics. The differential effects of cocaine self-administration on terminal function between core and shell is consistent with a region-specific functional reorganization of the mesolimbic DA system after repeated exposure and may provide an anatomical substrate for altered cognitive function after chronic drug-taking and addiction.

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One month of cocaine abstinence potentiates rapid dopamine signaling in the nucleus accumbens core

Cited by 16 publications

References 51 publications

Drug‐induced dysphoria is enhanced following prolonged cocaine abstinence and dynamically tracked by nucleus accumbens neurons

Drug‐induced dysphoria is enhanced following prolonged cocaine abstinence and dynamically tracked by nucleus accumbens neurons

Contrasting Regulation of Catecholamine Neurotransmission in the Behaving Brain: Pharmacological Insights from an Electrochemical Perspective

Terminal Dopamine Release Kinetics in the Accumbens Core and Shell Are Distinctly Altered after Withdrawal from Cocaine Self-Administration

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