Alterations in blood glucose levels under hyperinsulinemia affect accumbens dopamine

Bello, Nicholas T.; Hajnal, A.

doi:10.1016/j.physbeh.2006.03.027

Cited by 29 publications

(15 citation statements)

References 47 publications

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“…This is in keeping with previous findings where hypoglycemia increased dopamine release in the region [47] and 2DG evoked c-Fos in neurons in the area [4] although, a reduced dopamine turnover [48] has also been reported. Our data also support the idea that Ser31 activity is related to dopamine turnover in the brain [15].…”

Section: Discussionsupporting

confidence: 93%

Tyrosine Hydroxylase Phosphorylation in Catecholaminergic Brain Regions: A Marker of Activation following Acute Hypotension and Glucoprivation

et al. 2012

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The expression of c-Fos defines brain regions activated by the stressors hypotension and glucoprivation however, whether this identifies all brain sites involved is unknown. Furthermore, the neurochemicals that delineate these regions, or are utilized in them when responding to these stressors remain undefined. Conscious rats were subjected to hypotension, glucoprivation or vehicle for 30, 60 or 120 min and changes in the phosphorylation of serine residues 19, 31 and 40 in the biosynthetic enzyme, tyrosine hydroxylase (TH), the activity of TH and/or, the expression of c-Fos were determined, in up to ten brain regions simultaneously that contain catecholaminergic cell bodies and/or terminals: A1, A2, caudal C1, rostral C1, A6, A8/9, A10, nucleus accumbens, dorsal striatum and medial prefrontal cortex. Glucoprivation evoked phosphorylation changes in A1, caudal C1, rostral C1 and nucleus accumbens whereas hypotension evoked changes A1, caudal C1, rostral C1, A6, A8/9, A10 and medial prefrontal cortex 30 min post stimulus whereas few changes were evident at 60 min. Although increases in pSer19, indicative of depolarization, were seen in sites where c-Fos was evoked, phosphorylation changes were a sensitive measure of activation in A8/9 and A10 regions that did not express c-Fos and in the prefrontal cortex that contains only catecholaminergic terminals. Specific patterns of serine residue phosphorylation were detected, dependent upon the stimulus and brain region, suggesting activation of distinct signaling cascades. Hypotension evoked a reduction in phosphorylation in A1 suggestive of reduced kinase activity. TH activity was increased, indicating synthesis of TH, in regions where pSer31 alone was increased (prefrontal cortex) or in conjunction with pSer40 (caudal C1). Thus, changes in phosphorylation of serine residues in TH provide a highly sensitive measure of activity, cellular signaling and catecholamine utilization in catecholaminergic brain regions, in the short term, in response to hypotension and glucoprivation.

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Section: Discussionsupporting

confidence: 93%

Tyrosine Hydroxylase Phosphorylation in Catecholaminergic Brain Regions: A Marker of Activation following Acute Hypotension and Glucoprivation

et al. 2012

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“…However, as we did not find a significant RH treatment effect on mPFC dopamine on either days of testing, our data suggest that some other neurochemical system may underlie the effects of RH on set-shift performance, rather than dopamine. Consistent with this, one previous study has suggested that dopamine release (albeit under different conditions) is unaffected by alterations in brain glucose metabolism that persist for up to 80 minutes [54]. …”

Section: Discussionsupporting

confidence: 75%

Moderate Recurrent Hypoglycemia Markedly Impairs Set-Shifting Ability in a Rodent Model: Cognitive and Neurochemical Effects

Jahagirdar

Ramcharitar

Cotero

et al. 2012

TODIAJ

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Recurrent hypoglycemia (RH) is the major complication of intensive insulin treatment for diabetes mellitus. Of particular concern is the perceived potential for long-term impact of RH on cognition. Because diabetic patients have been reported to have deficits in mental flexibility and judgment, both generally considered to be mediated predominantly by the prefrontal cortex, the purpose of the present study was to determine whether RH would affect prefrontal cortex function. Medial prefrontal cortex (mPFC)-mediated set-shifting ability was tested in male Sprague-Dawley rats using a maze-based, food-reward Set-Shift task analogous to the Wisconsin card-sorting task. The performance measure was the number of trials to criterion on both day 1 (initial rule-learning) and day 2 (set-shifting in response to a changed contingency). In vivo microdialysis was used to measure mPFC extracellular glucose, lactate, pyruvate, glutamate, and dopamine. Post-mortem measures within the mPFC included glucose transporter 3 (GluT3) and c-Fos. RH animals had enhanced performance on day 1, consistent with previous work that showed RH to improve subsequent hippocampal function when euglycemic. The key finding of the present work is that RH led to impaired set-shifting performance on day 2, suggesting impairment in e.g. mental flexibility. Consistent with this finding, RH animals show decreased mPFC glycolysis on day 2 compared to controls. Our data show that RH can lead to subsequent impaired judgment, accompanied by reduced prefrontal cortex function. The findings suggest a potential underlying mechanism for the impaired judgment seen in diabetic patients.

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“…The striatum (i.e, the NAcc) contains neurons that sense glucose [88], expresses insulin receptors [89] and insulin action in the brain provides a negative feedback signal [90]. Moreover, insulin modulates dopamine signaling effectively reducing reinforcement potency [91, 92]. In humans, reduced insulin sensitivity is associated with less endogenous dopamine at D2/3 receptors in the NAcc and acute dopamine depletion, in turn, reduces insulin sensitivity [93].…”

Section: Endocrine Modulation Of Dopamine Signalingmentioning

confidence: 99%

Fuel not fun: Reinterpreting attenuated brain responses to reward in obesity

Kroemer

Small

2016

Physiology & Behavior

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There is a well-established literature linking obesity to altered dopamine signaling and brain response to food-related stimuli. Neuroimaging studies frequently report enhanced response in dopaminergic regions during food anticipation and decreased responses during reward receipt. This has been interpreted as reflecting anticipatory “reward surfeit”, and consummatory “reward deficiency”. In particular, attenuated response in the dorsal striatum to primary food rewards is proposed to reflect anhedonia, which leads to overeating in an attempt to compensate for the reward deficit. In this paper, we propose an alternative view. We consider brain response to food-related stimuli in a reinforcement-learning framework, which can be employed to separate the contributions of reward sensitivity and reward-related learning that are typically entangled in the brain response to reward. Consequently, we posit that decreased striatal responses to milkshake receipt reflect reduced reward-related learning rather than reward deficiency or anhedonia because reduced reward sensitivity would translate uniformly into reduced anticipatory and consummatory responses to reward. By re-conceptualizing reward deficiency as a shift in learning about subjective value of rewards, we attempt to reconcile neuroimaging findings with the putative role of dopamine in effort, energy expenditure and exploration and suggest that attenuated brain responses to energy dense foods reflect the “fuel”, not the fun entailed by the reward.

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Alterations in blood glucose levels under hyperinsulinemia affect accumbens dopamine

Cited by 29 publications

References 47 publications

Tyrosine Hydroxylase Phosphorylation in Catecholaminergic Brain Regions: A Marker of Activation following Acute Hypotension and Glucoprivation

Tyrosine Hydroxylase Phosphorylation in Catecholaminergic Brain Regions: A Marker of Activation following Acute Hypotension and Glucoprivation

Moderate Recurrent Hypoglycemia Markedly Impairs Set-Shifting Ability in a Rodent Model: Cognitive and Neurochemical Effects

Fuel not fun: Reinterpreting attenuated brain responses to reward in obesity

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