Opiate-Induced Molecular and Cellular Plasticity of Ventral Tegmental Area and Locus Coeruleus Catecholamine Neurons

Mazei-Robison, Michelle S.; Nestler, Eric J.

doi:10.1101/cshperspect.a012070

Cited by 94 publications

(69 citation statements)

References 100 publications

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“…Mouse VTA Nts neurons may instead contain either glutamate or GABA and project locally within the VTA to directly regulate DA neuron firing (Omelchenko and Sesack, 2009). Intriguingly, the small number of TH-negative Nts neurons was primarily detected in the caudal VTA along the rostral lateral borders, where the majority of VTA GABA neurons reside (Mazei-Robison and Nestler, 2012). These data suggest that mouse VTA Nts neurons could be GA-BAergic, and might provide local inhibitory control over neighboring DA neurons.…”

Section: Discussionmentioning

confidence: 99%

Determination of neurotensin projections to the ventral tegmental area in mice

et al. 2018

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Pharmacologic treatment with the neuropeptide neurotensin (Nts) modifies motivated behaviors such as feeding, locomotor activity, and reproduction. Dopamine (DA) neurons of the ventral tegmental area (VTA) control these behaviors, and Nts directly modulates the activity of DA neurons via Nts receptor-1. While Nts sources to the VTA have been described in starlings and rats, the endogenous sources of Nts to the VTA of mice remain incompletely understood, impeding determination of which Nts circuits orchestrate specific behaviors in this model. To overcome this obstacle we injected the retrograde tracer Fluoro-Gold into the VTA of mice that express GFP in Nts neurons. Identification of GFP-Nts cells that accumulate Fluoro-Gold revealed the Nts afferents to the VTA in mice. Similar to rats, most Nts afferents to the VTA of mice arise from the medial and lateral preoptic areas (POA) and the lateral hypothalamic area (LHA), brain regions that are critical for coordination of feeding and reproduction. Additionally, the VTA receives dense input from Nts neurons in the nucleus accumbens shell (NAsh) of mice, and minor Nts projections from the amygdala and periaqueductal gray area. Collectively, our data reveal multiple populations of Nts neurons that provide direct afferents to the VTA and which may regulate specific aspects of motivated behavior. This work lays the foundation for understanding endogenous Nts actions in the VTA, and how circuit-specific Nts modulation may be useful to correct motivational and affective deficits in neuropsychiatric disease.

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Section: Discussionmentioning

confidence: 99%

Determination of neurotensin projections to the ventral tegmental area in mice

et al. 2018

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“…Second, given the suppression of LC firing produced by autocrine release of galanin discussed earlier, one might predict that NE depletion would phenocopy increased galanin transmission; indeed, this is the case in many instances. For example, like transgenic galanin overexpression or galanin receptor agonist administration, selective suppression of NE transmission via knockout of α1-adrenergic receptors or the NE biosynthetic enzyme dopamine β-hydroxylase, 6-OHDA lesions, or the administration of adrenergic receptor antagonists can attenuate the rewarding effects of morphine and withdrawal symptoms (Drouin et al, 2002; Maldonado, 1997; Mazei-Robison and Nestler, 2012; Olson et al, 2006; Sahraei et al, 2004; Ventura et al, 2005; Weinshenker and Schroeder, 2007; Zarrindast et al, 2002). Similar to manipulations of galanin itself, suppression of NE transmission has no effect for the most part on operant psychostimulant self-administration, but we and others have shown that psychostimulant conditioned place preference and reinstatement are also reduced upon blockade of NE signaling (Leri et al, 2002; Mantsch et al, 2010; Schroeder et al, 2010; Schroeder et al, 2013; Smith and Aston-Jones, 2011; Ventura et al, 2007; Vranjkovic et al, 2014; Wee et al, 2008; Weinshenker and Schroeder, 2007; Zhang and Kosten, 2005; Zhang and Kosten, 2007) (our unpublished data).…”

Section: Addictionmentioning

confidence: 99%

Regulation of neurological and neuropsychiatric phenotypes by locus coeruleus-derived galanin

Weinshenker

Holmes

2016

Brain Research

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Decades of research confirm that noradrenergic locus coeruleus (LC) neurons are essential for arousal, attention, motivation, and stress responses. While most studies on LC transmission focused unsurprisingly on norepinephrine (NE), adrenergic signaling cannot account for all the consequences of LC activation. Galanin coexists with NE in the vast majority of LC neurons, yet the precise function of this neuropeptide has proved to be surprisingly elusive given our solid understanding of the LC system. To elucidate the contribution of galanin to LC physiology, here we briefly summarize the nature of stimuli that drive LC activity from a neuroanatomical perspective. We go on to describe the LC pathways in which galanin most likely exerts its effects on behavior, with a focus on addiction, depression, epilepsy, stress, and Alzheimer’s disease. We propose a model in which LC-derived galanin has two distinct functions: as a neuromodulator, primarily acting via the galanin 1 receptor (GAL1), and as a trophic factor, primarily acting via galanin receptor 2 (GAL2). Finally, we discuss how the recent advances in neuropeptide detection, optogenetics and chemical genetics, and galanin receptor pharmacology can be harnessed to identify the roles of LC-derived galanin definitively.

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“…Many studies focus on chronic drug administration (Harris and Aston-Jones, 1994; Hemby et al, 1995; Kaufling and Aston-Jones, 2015;Mazei-Robison and Nestler, 2012); however, it is unknown how drug exposure paired with withdrawal alters catecholamine signaling in regions associated with the addiction cycle. Since appetitive and aversive stimuli elicit opposing responses from catecholamines (Park et al, 2012;Roitman et al, 2008;Twining et al, 2015), we hypothesized dopamine and norepinephrine signal reciprocally during drug exposure and withdrawal.…”

Section: Introductionmentioning

confidence: 99%

Reciprocal Catecholamine Changes during Opiate Exposure and Withdrawal

Fox

Rodeberg

Wightman

2016

Neuropsychopharmacol

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Dysregulated catecholamine signaling has long been implicated in drug abuse. Although much is known about adaptations following chronic drug administration, little work has investigated how a single drug exposure paired with withdrawal influences catecholamine signaling in vivo. We used fast-scan cyclic voltammetry in freely moving rats to measure real-time catecholamine overflow during acute morphine exposure and naloxone-precipitated withdrawal in two regions associated with the addiction cycle: the dopamine-dense nucleus accumbens (NAc) and norepinephrine-rich ventral bed nucleus of the stria terminalis (vBNST). We compared dopamine transients in the NAc with norepinephrine concentration changes in the vBNST, and correlated release with specific withdrawal-related behaviors. Morphine increased dopamine transients in the NAc, but did not elicit norepinephrine responses in the vBNST. Conversely, dopamine output was decreased during withdrawal, while norepinephrine was released in the vBNST during specific withdrawal symptoms. Both norepinephrine and withdrawal symptoms could be elicited in the absence of morphine by administering naloxone with an α 2 antagonist. The data support reciprocal roles for dopamine and norepinephrine signaling during drug exposure and withdrawal. The data also support the allostasis model and show that negative-reinforcement may begin working after a single exposure/withdrawal episode.

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Opiate-Induced Molecular and Cellular Plasticity of Ventral Tegmental Area and Locus Coeruleus Catecholamine Neurons

Cited by 94 publications

References 100 publications

Determination of neurotensin projections to the ventral tegmental area in mice

Determination of neurotensin projections to the ventral tegmental area in mice

Regulation of neurological and neuropsychiatric phenotypes by locus coeruleus-derived galanin

Reciprocal Catecholamine Changes during Opiate Exposure and Withdrawal

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