Striatal dopamine transmission is reduced after chronic nicotine with a decrease in α6‐nicotinic receptor control in nucleus accumbens

Exley, Richard; Clements, Michael A.; Hartung, Henrike; McIntosh, J. Michael; Franklin, Michael; Bermúdez, Isabel; Cragg, Stephanie J.

doi:10.1111/ejn.12298

Cited by 33 publications

(37 citation statements)

References 42 publications

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“…In light of increased rates of smoking in mood disorders (Lasser et al, 2000;Lawrence et al, 2009) and emerging findings of the effects of nicotine on striatal functions (Exley et al, 2013), our results could be influenced by smoking status.…”

Section: Limitationsmentioning

confidence: 78%

Reward Processing in Unipolar and Bipolar Depression: A Functional MRI Study

Redlich

Dohm

Grotegerd

et al. 2015

Neuropsychopharmacol

143

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Differentiating bipolar disorders (BD) from unipolar depression (UD) remains a major clinical challenge. The identification of neurobiological markers may help to differentiate these disorders, particularly during depressive episodes. This cross-sectional study, including 33 patients with UD, 33 patients with BD, and 34 healthy controls, is one of the first to directly compare UD and BD with respect to reward processing. A card-guessing paradigm was employed and brain activity associated with reward processing was investigated by means of fMRI. A 3 (group) × 2 (condition: reward4control, loss4control) ANOVA was conducted using the nucleus accumbens (NAcc) as ROI. Furthermore, a whole-brain approach was applied. A functional connectivity analysis was performed to characterize diagnosis-related alterations in the functional coupling between the NAcc and other brain areas. The ANOVA revealed higher activity for healthy controls (HCs) than for BD and UD in the NAcc during reward processing. Moreover, UD showed a higher functional connectivity between the NAcc and the VTA than HC. The patients groups could be differentiated in that BD showed a decreased activation, in the reward condition, of the NAcc, caudate nucleus, thalamus, putamen, insula, and prefrontal areas compared with UD. These results may help to refine the understanding of neural correlates of reward processing in both disorders, and to understand the neural underpinnings of anhedonia, a core symptom of depressive episodes.

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Section: Limitationsmentioning

confidence: 78%

Reward Processing in Unipolar and Bipolar Depression: A Functional MRI Study

Redlich

Dohm

Grotegerd

et al. 2015

Neuropsychopharmacol

143

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“…Rodent SNc and ventral tegmental area (VTA) DA neurons express mRNAs for nAChR subunits α3–7 and β2–4 [273] and DA axons have diverse subtypes of heteropentameric β2-subunit-containing (β2*) nAChRs [274–277]. FCV studies using an α6-specific antagonist and subunit-specific knockout mice indicate that the nAChRs subtypes regulating DA release are α4α5β2 and α6β2β3 in CPu but α4α6β2β3 in NAc [276–280] (Figure 2). Non-β2*-nAChRs, i.e., homomeric α7-nAChRs, have not been identified on DA axons; however.…”

Section: Regulation Of Dopamine Releasementioning

confidence: 99%

Striatal dopamine neurotransmission: Regulation of release and uptake

2016

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Dopamine (DA) transmission is governed by processes that regulate release from axonal boutons in the forebrain and the somatodendritic compartment in midbrain, and by clearance by the DA transporter, diffusion, and extracellular metabolism. We review how axonal DA release is regulated by neuronal activity and by autoreceptors and heteroreceptors, and address how quantal release events are regulated in size and frequency. In brain regions densely innervated by DA axons, DA clearance is due predominantly to uptake by the DA transporter, whereas in cortex, midbrain, and other regions with relatively sparse DA inputs, the norepinephrine transporter and diffusion are involved. We discuss the role of DA uptake in restricting the sphere of influence of DA and in temporal accumulation of extracellular DA levels upon successive action potentials. The tonic discharge activity of DA neurons may be translated into a tonic extracellular DA level, whereas their bursting activity can generate discrete extracellular DA transients.

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“…Interestingly, administration of nicotine results in similar changes in the α4β2* and α6β2* nAChRs levels, and to a similar magnitude as that obtained in the present study with sucrose (Renda and Nashmi, 2014, Exley et al, 2013, Perez et al, 2013. Although the mechanisms responsible for this are still not fully understood, it has been suggested that changes in α4β2* and α6β2* nAChRs contribute to nicotine re-enforcement and self-administration (Madsen et al, 2014, Picciotto and Kenny, 2013, Leslie et al, 2013, De Biasi and Dani, 2011.…”

Section: Discussionsupporting

confidence: 87%

The Effects of Binge-Like Sucrose Consumption on the Mesolimbic Reward Pathway in the Brain

Shariff¹

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Obesity is becoming a worldwide epidemic (WHO, 2000, Leigh and Morris, 2016, Lifshitz and Lifshitz, 2014, James, 2004. Pharmacotherapeutics that attempt to stem overweight and obesity have largely been ineffective and often are accompanied by adverse side effects (Glazer, 2001). It is therefore imperative to develop effective strategies to combat obesity. A paradigm that has gained momentum relatively recently is the development of addiction to fat and sweet food (Fortuna, 2012, Smith and Robbins, 2013, Volkow et al., 2013a. While drugs of abuse affect various brain subregions, they have been shown to act on three major areas of the brain, namely the brain stem, the limbic system and the cerebral cortex (NIDA, 2010).The limbic system is an interconnected collection of brain structures such as the nucleus accumbens (NAc) and the basolateral amygdala (BLA), whose neural connectivities encode emotional states such as anticipation of reward and motivation (Berridge, 2012). At the molecular level, in addition to the various dysregulatory outcomes in relation to neurotransmitters, it is the dysregulation of balance between dopamine (DA) and acetylcholine (ACh) in the limbic system, especially in the NAc that has been found to drive and maintain behaviours that perpetuate addiction to substances of abuse (Hoebel et al., 2007, Aosaki et al., 2010. Interestingly, sucrose, a potent contributor to the development of obesity (Lakhan and Kirchgessner, 2013, Tappy et al., 2010), has been shown, albeit indirectly, to affect the release of DA in the NAc via the nAChRs (Avena et al., 2008). The role of specific subtypes of nAChRs in the NAc has yet to be elucidated in relation to sucrose consumption.Firstly, this study establishes that the nAChRs are involved in regulating sucrose consumption. Based on the various nAChRs agonists/partial agonists and antagonists tested systemically, it is surmised that *nAChRs are involved in mediating sucrose consumption.Furthermore, coupled to the changes in nAChRs, this study also sheds light for the first time ii on the global morphological changes that occur in the dendrites of the neurons in the NAc and BLA reminiscent of similar changes due to drugs of abuse, suggestive of a global imbalance at the level of the NAc and amygdala. Further studies are warranted to determine the precise functional significance of the morphological changes that are reported in this study, and to discover potential newer pharmacotherapies that target the nAChRs. At the present time, however, varenicline, an FDA approved pharmacotherapeutic, appears to be an attractive agent in reducing sucrose intake. Varenicline may hold potential benefits in lowering weight gain thus concomitantly lowering the global burden of obesity-related disease.iii

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Striatal dopamine transmission is reduced after chronic nicotine with a decrease in α6‐nicotinic receptor control in nucleus accumbens

Cited by 33 publications

References 42 publications

Reward Processing in Unipolar and Bipolar Depression: A Functional MRI Study

Reward Processing in Unipolar and Bipolar Depression: A Functional MRI Study

Striatal dopamine neurotransmission: Regulation of release and uptake

The Effects of Binge-Like Sucrose Consumption on the Mesolimbic Reward Pathway in the Brain

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