Regulation of the mesocorticolimbic and mesostriatal dopamine systems by α-melanocyte stimulating hormone and agouti-related protein

Roseberry, Aaron G.; Stuhrman, Katherine; Dunigan, Anna I.

doi:10.1016/j.neubiorev.2015.06.020

Cited by 53 publications

(33 citation statements)

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“…Nuclei of the amygdala, most notably the MeApd (that is implicated in self-grooming 52 ), also project to the medial hypothalamus 47 . Finally, the hypothalamic–pituitary system has now been implicated in the modulation of self-grooming, as several hypothalamic and pituitary hormones (including the stress-related peptides corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH)) are known to induce self-grooming 55–58 (see Supplementary information S3 (table)). The effects of these hormones on grooming are partly dependent on the mesolimbic dopaminergic system 59–61 (as we emphasize below).…”

Section: Neurobiology Of Rodent Self-groomingmentioning

confidence: 99%

Neurobiology of rodent self-grooming and its value for translational neuroscience

Stewart²,

et al. 2015

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Self-grooming is a complex innate behaviour with an evolutionary conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders — including models of autism spectrum disorder and obsessive compulsive disorder — that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action.

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Section: Neurobiology Of Rodent Self-groomingmentioning

confidence: 99%

Neurobiology of rodent self-grooming and its value for translational neuroscience

Stewart²,

et al. 2015

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“…This system encompasses two neuronal populations in the arcuate nucleus of the hypothalamus: pro‐opiomelanocortin (POMC) expressing neurons and agouti‐related protein/neuropeptide‐Y (AgRP/NPY) expressing neurons, as well as the peptides released by these neurons and the downstream receptors of these peptides (Roseberry et al . ). POMC is a propeptide that is post‐translationally processed to produce the melanocyte‐stimulating hormones (α‐, β‐, and γ‐MSH).…”

Section: Introductionmentioning

confidence: 97%

“…α‐, β‐, and γ‐MSH are agonists to the centrally expressed melanocortin receptors, melanocortin‐3 and melanocortin‐4 receptors (MC3/4Rs), whereas AgRP is an inverse‐agonist to the MC3/4Rs (Roseberry et al . ). AgRP/NPY and POMC neurons respond to the energy state of an animal and function in an opposing manner.…”

Section: Introductionmentioning

confidence: 97%

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Alpha‐melanocyte stimulating hormone increases the activity of melanocortin‐3 receptor‐expressing neurons in the ventral tegmental area

West

Lü

Olson

et al. 2019

The Journal of Physiology

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Key points Alpha‐melanocyte stimulating hormone (α‐MSH) is an anorexigenic peptide. Injection of the α‐MSH analog MTII into the ventral tegmental area (VTA) decreases food and sucrose intake and food reward. Melanocortin‐3 receptors (MC3R) are highly expressed in the VTA, suggesting that the effects of intra‐VTA α‐MSH may be mediated by α‐MSH changing the activity of MC3R‐expressing VTA neurons. α‐MSH increased the firing rate of MC3R VTA neurons in acute brain slices from mice, although it did not affect the firing rate of non‐MC3R VTA neurons. The α‐MSH induced increase in MC3R neuron firing rate is probably activity‐dependent, and was independent of fast synaptic transmission and intracellular Ca2+ levels. These results help us to better understand how α‐MSH acts in the VTA to affect feeding and other dopamine‐dependent behaviours. Abstract The mesocorticolimbic dopamine system, the brain's reward system, regulates multiple behaviours, including food intake and food reward. There is substantial evidence that the melanocortin system of the hypothalamus, an important neural circuit controlling feeding and body weight, interacts with the mesocorticolimbic dopamine system to affect feeding, food reward and body weight. For example, melanocortin‐3 receptors (MC3Rs) are expressed in the ventral tegmental area (VTA) and our laboratory previously showed that intra‐VTA injection of the MC3R agonist, MTII, decreases home‐cage food intake and operant responding for sucrose pellets. However, the cellular mechanisms underlying the effects of intra‐VTA alpha‐melanocyte stimulating hormone (α‐MSH) on feeding and food reward are unknown. To determine how α‐MSH acts in the VTA to affect feeding, we performed electrophysiological recordings in acute brain slices from mice expressing enhanced yellow fluorescent protein in MC3R neurons to test how α‐MSH affects the activity of VTA MC3R neurons. α‐MSH significantly increased the firing rate of VTA MC3R neurons without altering the activity of non‐MC3R expressing VTA neurons. In addition, the α‐MSH‐induced increase in MC3R neuron activity was independent of fast synaptic transmission and intracellular Ca2+ levels. Finally, we show that the effect of α‐MSH on MC3R neuron firing rate is probably activity‐dependent. Overall, these studies provide an important advancement in the understanding of how α‐MSH acts in the VTA to affect feeding and food reward.

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“…Receptor stimulation leads to increased dopamine release and turn over in mesolimbic brain areas and decreased food‐seeking behaviours and preference for high‐fat foods in animals . In the absence of MC4R signalling, low dopamine levels and associated hyperphagia would be expected . Indeed, hyperphagia in MC4R deficient rats/mice improves with selective restoration of MC4R signalling in the mesolimbic system, and imaging studies in leptin deficient humans show changes in brain activity in response to leptin substitution predominantly in the dopaminergic brain areas …”

Section: Discussionmentioning

confidence: 99%

Methylphenidate in children with monogenic obesity due to LEPR or MC4R deficiency improves feeling of satiety and reduces BMI‐SDS—A case series

Brandt¹,

Schnurbein²,

Lennerz

et al. 2019

Pediatric Obesity

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Summary Background The clinical phenotype of patients with monogenic obesity due to mutations in the leptin receptor (LEPR) or melanocortin 4 receptor (MC4R) gene is characterized by impaired satiety and hyperphagia, leading to extreme, sometimes life‐threatening weight gain. Subjects/methods In a case series, we analysed the effect of an off‐label methylphenidate (MPH) use for 1 year as an individual treatment approach on eating behaviour (Child Eating Behaviour Questionnaire [CEBQ]), appetite (visual analogue scales) and body mass index (BMI) trajectories in five patients with severe obesity due to mutations in the LEPR (n = 3) or MC4R (n = 2) gene. Results After 1 year use of MPH (20 mg/day divided in two to three doses), BMI (Δ BMIT0−T1 truex¯: −0.7 ± 0.9 kg/m2), BMI standard deviation score (SDS) (Δ BMI‐SDST0−T1 truex¯: −0.32 ± 0.20), and %BMIP95 (Δ %BMIP95T0−T1 truex¯: −6.6 ± 7.8%) decreased. BMI‐SDS velocity decreased from +0.17 ± 0.22 to −0.30 ± 0.20. Appetite and CEBQ subscale scores for “food responsiveness” and “enjoyment of food” decreased. We observed adverse effects with increase in self‐reported frequency of disordered sleep, nervousness, hyperactivity, and tics. Conclusions The observed decrease in BMI trajectories with MPH use for one year is clinically meaningful in this group of patients, since the natural course would have been associated with a pronounced increase in BMI, leading to comorbidities and complications over time.

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Regulation of the mesocorticolimbic and mesostriatal dopamine systems by α-melanocyte stimulating hormone and agouti-related protein

Cited by 53 publications

References 100 publications

Neurobiology of rodent self-grooming and its value for translational neuroscience

Neurobiology of rodent self-grooming and its value for translational neuroscience

Alpha‐melanocyte stimulating hormone increases the activity of melanocortin‐3 receptor‐expressing neurons in the ventral tegmental area

Methylphenidate in children with monogenic obesity due to LEPR or MC4R deficiency improves feeling of satiety and reduces BMI‐SDS—A case series

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