Effects of Cocaine and Pimozide on Plasma and Brain Alpha-Melanocyte-Stimulating Hormone Levels in Rats

Sarnyai, Zoltán; Vecsernyés, Miklós; Julesz, J.; Szabó, Gyula; Telegdy, Gyula

doi:10.1159/000126090

Cited by 9 publications

(4 citation statements)

References 8 publications

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“…Meanwhile, decreasing MC4R enhances glutamatergic signaling in the striatum 17 . Given that dopamine agonists increase POMC, the precursor for α-MSH 42 , and cocaine increases striatal α-MSH content 43 , rewarding events may result in α-MSH-MC4R binding. This binding would cause GluA2-AMPAR internalization, decreasing the synaptic sensitivity of DMS MSNs to cortico-striatal glutamatergic afferents, which otherwise trigger response plasticity and suppression in many contexts 44 – 46 .…”

Section: Discussionmentioning

confidence: 99%

Inter-individual variability amplified through breeding reveals control of reward-related action strategies by Melanocortin-4 Receptor in the dorsomedial striatum

et al. 2022

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In day-to-day life, we often must choose between pursuing familiar behaviors or adjusting behaviors when new strategies might be more fruitful. The dorsomedial striatum (DMS) is indispensable for arbitrating between old and new action strategies. To uncover molecular mechanisms, we trained mice to generate nose poke responses for food, then uncoupled the predictive relationship between one action and its outcome. We then bred the mice that failed to rapidly modify responding. This breeding created offspring with the same tendencies, failing to inhibit behaviors that were not reinforced. These mice had less post-synaptic density protein 95 in the DMS. Also, densities of the melanocortin-4 receptor (MC4R), a high-affinity receptor for α-melanocyte-stimulating hormone, predicted individuals’ response strategies. Specifically, high MC4R levels were associated with poor response inhibition. We next found that reducing Mc4r in the DMS in otherwise typical mice expedited response inhibition, allowing mice to modify behavior when rewards were unavailable or lost value. This process required inputs from the orbitofrontal cortex, a brain region canonically associated with response strategy switching. Thus, MC4R in the DMS appears to propel reward-seeking behavior, even when it is not fruitful, while moderating MC4R presence increases the capacity of mice to inhibit such behaviors.

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Section: Discussionmentioning

confidence: 99%

Inter-individual variability amplified through breeding reveals control of reward-related action strategies by Melanocortin-4 Receptor in the dorsomedial striatum

et al. 2022

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“…However, it may be that loss of melanocortins in Pomc -/- mice are exerting an effect upon the central rewarding system to favour fat consumption. Given the localization of POMC and MC4-R in brain reward regions (33-35) and functional interactions with psychostimulants (36;37), there is certainly evidence indicating melanocortins may have a role beyond that of helping to integrate a response to nutrient sensing. Genetically modified mice with selective loss of POMC fragments in specific brain regions may be useful to bring about a fuller clarification of such hypotheses.…”

Section: Discussionmentioning

confidence: 99%

Pro-Opiomelanocortin Modulates the Thermogenic and Physical Activity Responses to High-Fat Feeding and Markedly Influences Dietary Fat Preference

et al. 2007

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Complete proopiomelanocortin (POMC) deficiency causes a human syndrome of hypoadrenalism, altered skin and hair pigmentation, and severe hyperphagic obesity. Heterozygote carriers of nonsense mutations are strongly predisposed to obesity. Pomc(+/-) mice have normal body weight on a chow diet but increase food intake and become more obese than wild-type littermates when placed on a high-fat diet. To further explore the mechanisms whereby dietary fat interacts with Pomc genotype to produce obesity, we examined Pomc-null, Pomc(+/-), and wild-type mice for changes in the components of energy balance in response to provision of a high-fat diet and macronutrient preference when presented with a selection of dietary choices. In contrast to wild-type mice, Pomc null mice did not increase their resting energy expenditure or their spontaneous physical activity when given a high-fat diet. Pomc(+/-) mice increased resting energy expenditure similarly to wild types, but their increase in physical activity was significantly less than that seen in wild-type mice. In two independent experimental tests of macronutrient preference, Pomc genotype was a strong predictor of dietary fat preference with Pomc null animals choosing to eat approximately twice as much fat, but similar amounts of carbohydrate and protein, as wild-type animals. Pomc(+/-) mice showed an intermediate response. In summary, POMC-derived peptides have influences on multiple aspects of the organism's response to the presentation of high-fat diet. This includes a major influence, readily discernible even in heterozygote animals, on the dietary preference for fat.

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“…In addition, in vitro studies demonstrate that α‐MSH stimulates cAMP production via interactions with dopamine D1 receptors (Lezcano et al ., 1995; Cremer et al ., 2000). Activation of dopamine neurotransmission, by administration of either a direct‐acting dopamine agonist or an indirect agonist like cocaine, is also reported to upregulate POMC expression in the arcuate nucleus and melanocortin neuropeptide levels in nucleus accumbens (Sarnyai et al ., 1992; Tong & Pelletier, 1992). Finally, one recent study demonstrated that infusion of a melanocortin agonist into the lateral ventricle enhances the effects of amphetamine on lateral hypothalamic self‐stimulation (Cabeza de Vaca et al ., 2002).…”

Section: Introductionmentioning

confidence: 99%

Blockade of melanocortin transmission inhibits cocaine reward

Hsu¹,

Taylor²,

Newton³

et al. 2005

Eur J of Neuroscience

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Melanocortins and the melanocortin-4 receptor (MC4-R) are enriched in the nucleus accumbens, a brain region that has been implicated in the rewarding action of cocaine and other drugs of abuse. In the present study we use a number of rat behavioral models to show that infusion of a melanocortin peptide antagonist into the nucleus accumbens blocks the reinforcing, incentive motivational, and locomotor sensitizing effects of cocaine. We also show that locomotor responses to repeated cocaine exposure are completely blocked in MC4-R null mutant mice and reduced in Agouti mice that overexpress an endogenous inhibitor of melanocortins in the brain. The results also demonstrate that cocaine administration increases the expression of MC4-R in the nucleus accumbens and striatum, and that MC4-R is co-localized with prodynorphin in medium spiny neurons in the nucleus accumbens. Together, these findings indicate that the behavioral actions of cocaine are dependent on activation of MC4-R, and suggest that upregulation of this receptor by drug exposure may contribute to sensitization of these behavioral responses. Modulation of cocaine reward is a novel action of the melanocortin-MC4-R system and could be targeted for the development of new medications for cocaine addiction.

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Effects of Cocaine and Pimozide on Plasma and Brain Alpha-Melanocyte-Stimulating Hormone Levels in Rats

Cited by 9 publications

References 8 publications

Inter-individual variability amplified through breeding reveals control of reward-related action strategies by Melanocortin-4 Receptor in the dorsomedial striatum

Inter-individual variability amplified through breeding reveals control of reward-related action strategies by Melanocortin-4 Receptor in the dorsomedial striatum

Pro-Opiomelanocortin Modulates the Thermogenic and Physical Activity Responses to High-Fat Feeding and Markedly Influences Dietary Fat Preference

Blockade of melanocortin transmission inhibits cocaine reward

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