Infusion of fluoxetine, a serotonin reuptake inhibitor, in the shell region of the nucleus accumbens increases blood glucose concentrations in rats

Diepenbroek, Charlene; Rijnsburger, Merel; Eggels, Leslie; Megen, Kayleigh M. van; Ackermans, Mariëtte T.; Fliers, Eric; Kalsbeek, Andries; Serlie, Mireille J.; Fleur, Susanne E. la

doi:10.1016/j.neulet.2016.11.045

Cited by 13 publications

(12 citation statements)

References 28 publications

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“…Nevertheless, consistent with our findings, two recent studies reported blood glucose changes following either electrical stimulation (Diepenbroek et al, 2013) or serotonin reuptake inhibition (Diepenbroek et al, 2016) specifically in the NAc shell. These observations, in concert with the rest of our results, extend prior findings implicating striatal D2R in food learning flexibility (Haluk and Floresco, 2009;Kruzich et al, 2006;Yawata et al, 2012) and compulsive-like, perseverative feeding (Halpern et al, 2013;Yawata et al, 2012) by implicating involvement of D2R signaling in such behaviors via integration of glucose metabolic signaling and glucose-derived reinforcement learning mechanisms.…”

Section: Discussionsupporting

confidence: 93%

“…Although D2R signaling in the NAc shell is known to modulate a variety of reinforcement learningrelated behaviors (Kenny et al, 2013;Kravitz and Kreitzer, 2012;Lobo and Nestler, 2011;Yawata et al, 2012), involvement of NAc D2R signaling in glucose metabolic regulation has not, to our knowledge, been previously reported. Notably, the specific DARPP-32 manipulation we used here would not be limited to selectively affecting D2R signaling in these neurons but also signaling relevant to other sites such as serotonin receptors (Diepenbroek et al, 2016;Lindskog, 2008). In fact, this may provide an explanation for the differences in glucose tolerance profiles that we observed in D32 fl/fl /D2cre + mice as compared with mice injected with D2R ligands directly into NAc shell.…”

Section: Discussionmentioning

confidence: 99%

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Dopamine D2 Receptor Signaling in the Nucleus Accumbens Comprises a Metabolic–Cognitive Brain Interface Regulating Metabolic Components of Glucose Reinforcement

Michaelides

Miller

DiNieri

et al. 2017

Neuropsychopharmacol

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Appetitive drive is influenced by coordinated interactions between brain circuits that regulate reinforcement and homeostatic signals that control metabolism. Glucose modulates striatal dopamine (DA) and regulates appetitive drive and reinforcement learning. Striatal DA D2 receptors (D2Rs) also regulate reinforcement learning and are implicated in glucose-related metabolic disorders. Nevertheless, interactions between striatal D2R and peripheral glucose have not been previously described. Here we show that manipulations involving striatal D2R signaling coincide with perseverative and impulsive-like responding for sucrose, a disaccharide consisting of fructose and glucose. Fructose conveys orosensory (ie, taste) reinforcement but does not convey metabolic (ie, nutrient-derived) reinforcement. Glucose however conveys orosensory reinforcement but unlike fructose, it is a major metabolic energy source, underlies sustained reinforcement, and activates striatal circuitry. We found that mice with deletion of dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) exclusively in D2R-expressing cells exhibited preferential D2R changes in the nucleus accumbens (NAc), a striatal region that critically regulates sucrose reinforcement. These changes coincided with perseverative and impulsive-like responding for sucrose pellets and sustained reinforcement learning of glucose-paired flavors. These mice were also characterized by significant glucose intolerance (ie, impaired glucose utilization). Systemic glucose administration significantly attenuated sucrose operant responding and D2R activation or blockade in the NAc bidirectionally modulated blood glucose levels and glucose tolerance. Collectively, these results implicate NAc D2R in regulating both peripheral glucose levels and glucose-dependent reinforcement learning behaviors and highlight the notion that glucose metabolic impairments arising from disrupted NAc D2R signaling are involved in compulsive and perseverative feeding behaviors.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Dopamine D2 Receptor Signaling in the Nucleus Accumbens Comprises a Metabolic–Cognitive Brain Interface Regulating Metabolic Components of Glucose Reinforcement

Michaelides

Miller

DiNieri

et al. 2017

Neuropsychopharmacol

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“…In animals, stimulation of the NAc shell increases concentrations of both dopamine and serotonin (58,59). It is currently unknown whether DBS in this region induces serotonin release in humans, but evidence from multiple species supports a role for serotonin signaling in the control of glucose metabolism (60)(61)(62)(63). Other neurotransmitters, including glutamate and GABA (-aminobutyric acid) (64)(65)(66), are also affected by DBS of the NAc area and may be involved in its glucoregulatory effects.…”

Section: Discussionmentioning

confidence: 99%

Striatal dopamine regulates systemic glucose metabolism in humans and mice

et al. 2018

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The brain is emerging as an important regulator of systemic glucose metabolism. Accumulating data from animal and observational human studies suggest that striatal dopamine signaling plays a role in glucose regulation, but direct evidence in humans is currently lacking. We present a series of experiments supporting the regulation of peripheral glucose metabolism by striatal dopamine signaling. First, we present the case of a diabetes patient who displayed strongly reduced insulin requirements after treatment with bilateral deep brain stimulation (DBS) targeting the anterior limb of the internal capsule. Next, we show that DBS in this striatal area, which induced dopamine release, increased hepatic and peripheral insulin sensitivity in 14 nondiabetic patients with obsessive-compulsive disorder. Conversely, systemic dopamine depletion reduced peripheral insulin sensitivity in healthy subjects. Supporting these human data, we demonstrate that optogenetic activation of dopamine D receptor-expressing neurons in the nucleus accumbens increased glucose tolerance and insulin sensitivity in mice. Together, these findings support the hypothesis that striatal neuronal activity regulates systemic glucose metabolism.

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“…In addition to all the above-mentioned functions, 5-HT also plays a regulatory role in the metabolic processes in NAc, leading to an increase in glucose blood levels [149]. Studies show, on the one hand, the significant role of 5-HT in the regulation of several processes controlled by NAc.…”

Section: Serotoninergic Systemmentioning

confidence: 99%

Neuroplasticity and Multilevel System of Connections Determine the Integrative Role of Nucleus Accumbens in the Brain Reward System

Bayassi-Jakowicka

Lietzau

Czuba

et al. 2021

IJMS

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A growing body of evidence suggests that nucleus accumbens (NAc) plays a significant role not only in the physiological processes associated with reward and satisfaction but also in many diseases of the central nervous system. Summary of the current state of knowledge on the morphological and functional basis of such a diverse function of this structure may be a good starting point for further basic and clinical research. The NAc is a part of the brain reward system (BRS) characterized by multilevel organization, extensive connections, and several neurotransmitter systems. The unique role of NAc in the BRS is a result of: (1) hierarchical connections with the other brain areas, (2) a well-developed morphological and functional plasticity regulating short- and long-term synaptic potentiation and signalling pathways, (3) cooperation among several neurotransmitter systems, and (4) a supportive role of neuroglia involved in both physiological and pathological processes. Understanding the complex function of NAc is possible by combining the results of morphological studies with molecular, genetic, and behavioral data. In this review, we present the current views on the NAc function in physiological conditions, emphasizing the role of its connections, neuroplasticity processes, and neurotransmitter systems.

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Infusion of fluoxetine, a serotonin reuptake inhibitor, in the shell region of the nucleus accumbens increases blood glucose concentrations in rats

Cited by 13 publications

References 28 publications

Dopamine D2 Receptor Signaling in the Nucleus Accumbens Comprises a Metabolic–Cognitive Brain Interface Regulating Metabolic Components of Glucose Reinforcement

Dopamine D2 Receptor Signaling in the Nucleus Accumbens Comprises a Metabolic–Cognitive Brain Interface Regulating Metabolic Components of Glucose Reinforcement

Striatal dopamine regulates systemic glucose metabolism in humans and mice

Neuroplasticity and Multilevel System of Connections Determine the Integrative Role of Nucleus Accumbens in the Brain Reward System

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