Cocaine- and Amphetamine-Regulated Transcript Peptide Plays a Role in the Manifestation of Depression: Social Isolation and Olfactory Bulbectomy Models Reveal Unifying Principles

Dandekar, Manoj P.; Singru, Praful S.; Kokare, Dadasaheb M.; Subhedar, Nishikant K.

doi:10.1038/npp.2008.201

Cited by 64 publications

(37 citation statements)

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“…Several theories have been proposed to explain the increased food intake and body weight following social isolation. The social isolation of rats in early or adult life produced a chronic psychological stress or depression, 18,[40][41][42] and such condition resulted in the increased food consumption and deleterious weight gain. 43,44 However, in this study, basal plasma cortisol levels, a key stress indicator 21,22 in the socially isolated rats did not change.…”

Section: Discussionmentioning

confidence: 99%

“…31 The detailed procedure of cannulation and injections has been described earlier. 18,24 After cannulation, those rats losing 410% of body weight during recovery period of 7 days were discarded. 32,33 Intracerebroventricular (i.c.v.)…”

Section: Animalsmentioning

confidence: 99%

“…28,30 Such condition increases the risk of development of atypical depression that accompanies hyperphagia and weight gain. 1,2,8,18 The rats were housed in acrylic cages (24 Â 17 Â 12 cm) under a constant room temperature (25 ± 2 1C), relative humidity (50 ± 5%) and maintained under a controlled 12:12 h dark-light cycle (lights on at 0000 h). Rat chow food pellets (provide 3.30 kcal g -1 with 72.1% carbohydrate, 23.4% protein and 4.5% fat) and drinking water were available ad libitum.…”

Section: Animalsmentioning

confidence: 99%

“…[10][11][12] Social isolation is known to induce profound changes in a range of endogenous neurotransmitter systems. Increased serotonin 13 and neuropeptide Y 14 levels and decreased dopamine, noradrenaline, 15 neurosteroids, 16 a-melanocyte-stimulating hormone 17 and cocaine-and amphetamine-regulated transcript peptide (CART) 18 contents were noticed following social isolation. However, the precise neuronal mechanisms that link social isolation with hyperphagia and body weight gain are yet to be understood.…”

Section: Introductionmentioning

confidence: 99%

“…Social isolation resulted in decreased CART immunoreactivity in the hypothalamic arcuate (ARC) and paraventricular nuclei (PVN), Edinger-Westphal neurons and fibers of the central nucleus of amygdala and locus coeruleus, and the changes were correlated to depression. 18 As hyperphagia and body weight gain are known to be the major consequences of depression, 1,2 we wanted to explore the possibility that CART may be involved in the social isolation-induced increase in food intake and body weight. To test the hypothesis, naive male rats were individually housed for 6 weeks, and during this period, they were administered with CART (54-102) and the effects on food intake and body weight were monitored.…”

Section: Introductionmentioning

confidence: 99%

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Central regulation of feeding behavior during social isolation of rat: evidence for the role of endogenous CART system

et al. 2010

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Objective: Although hyperphagia and body weight gain are well-recognized consequences of social isolation, the underlying mechanisms are not understood. The aim of this work is to test the possibility that the endogenous cocaine-and amphetamineregulated transcript peptide (CART) may be involved in the process. Design: Socially isolated rats were screened for increase in food intake and body weight, and the modifications of these parameters by CART were evaluated. Furthermore, isolated animals were re-socialized and screened for reversal of these effects. Response of the endogenous CART system, in certain hypothalamic nuclei of the isolated and re-socialized rats, was evaluated with immunohistochemistry. Subjects: Fifty days old naive male Sprague-Dawley rats were used. Measurements: The effects of CART/CART antibody on the social isolation and subsequent re-socialization on feeding and body weight changes were monitored. Moreover, the immunohistochemical response of endogenous CART system to social isolation and re-socialization was analyzed morphometrically. Results: While social isolation of rats for a period of 6 weeks caused progressive increase in food consumption and body weight gain, these rats showed a significant reduction in food intake and body weight when injected daily with CART via intracerebroventricular (i.c.v.) route, for the following 7 days. The re-socialization of isolated rats reduced food intake and body weight to the control levels. These effects of re-socialization were attenuated by immunoneutralization of the endogenous CART by i.c.v. CART antibody. Social isolation also resulted in a drastic reduction in CART immunoreactivity in the cells and/or fibers in the hypothalamic areas like dorsomedial, ventromedial, lateral, paraventricular and arcuate nuclei, recognized for their role in feeding. On the other hand, the CART immunoreactivity profile was fully restored following 7 days of re-socialization of the isolation-reared rats. Conclusion: Social isolation might down-regulate the hypothalamic CART-containing system, which in turn may lead to increase in food intake and body weight.

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Section: Discussionmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Central regulation of feeding behavior during social isolation of rat: evidence for the role of endogenous CART system

et al. 2010

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Ontogeny of the cocaine‐ and amphetamine‐regulated transcript (CART) neuropeptide system in the brain of zebrafish, Danio rerio

Mukherjee¹,

Subhedar²,

Ghose³

2012

J of Comparative Neurology

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The cocaine- and amphetamine-regulated transcript (CART) peptidergic system is involved in processing diverse neuronal functions in adult animals, including energy metabolism. Although CART is widely distributed in the brain of a range of vertebrates, the ontogeny of this system has not been explored. The CART-immunoreactive system in the zebrafish central nervous system (CNS) was studied across developmental stages until adulthood. The peptide is expressed as early as 24 hours post fertilization and establishes itself in several discrete areas of the brain and spinal cord as development progresses. The trends in CART ontogeny suggest that it may be involved in the establishment of commissural tracts, typically expressing early but subsequently decaying. CART elements are commonly overrepresented in diverse sensory areas like the olfactory, photic, and acoustico-mechanosensory systems, perhaps indicating a role for the peptide in sensory perception. Key neuroendocrine centers, like the preoptic area, hypothalamus, and pituitary, conspicuously show CART innervations, suggesting functions analogous to those demonstrated in other chordates. Uniquely, the epiphysis also appears to employ CART as a neurotransmitter. The entopeduncular nucleus is a major CART-containing group in the adult teleost forebrain that may participate in glucose sensing. This region responds to glucose in the 15-day larvae, suggesting that the energy status sensing CART circuits is active early in development. The pattern of CART expression in zebrafish suggests conserved evolutionary trends among vertebrate species. Developmental expression profiling reveals putative novel functions and establishes zebrafish as a model to investigate CART function in physiology and development.

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Differential distribution and energy status–dependent regulation of the four CART neuropeptide genes in the zebrafish brain

Akash

Kaniganti

Tiwari

et al. 2014

J of Comparative Neurology

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The cocaine- and amphetamine-regulated transcript (CART) neuropeptide has been implicated in the neural regulation of energy homeostasis across vertebrate phyla. By using gene-specific in situ hybridization, we have mapped the distribution of the four CART mRNAs in the central nervous system of the adult zebrafish. The widespread neuronal expression pattern for CART 2 and 4 suggests a prominent role for the peptide in processing sensory information from diverse modalities including olfactory and visual inputs. In contrast, CART 1 and 3 have a much more restricted distribution, predominantly located in the nucleus of the medial longitudinal fasciculus (NMLF) and entopeduncular nucleus (EN), respectively. Enrichment of CART 2 and 4 in the preoptic and tuberal areas emphasizes the importance of CART in neuroendocrine functions. Starvation resulted in a significant decrease in CART-positive cells in the nucleus recessus lateralis (NRL) and nucleus lateralis tuberis (NLT) hypothalamic regions, suggesting a function in energy homeostasis for these neurons. Similarly, the EN emerges as a novel energy status-responsive region. Not only is there abundant and overlapping expression of CART 2, 3, and 4 in the EN, but also starvation induced a decrease in CART-expressing neurons in this region. The cellular resolution mapping of CART mRNA and the response of CART-expressing nuclei to starvation underscores the importance of CART neuropeptide in energy processing. Additionally, the regional and gene-specific responses to energy levels suggest a complex, interactive network whereby the four CART gene products may have nonredundant functions in energy homeostasis.

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Cocaine- and Amphetamine-Regulated Transcript Peptide Plays a Role in the Manifestation of Depression: Social Isolation and Olfactory Bulbectomy Models Reveal Unifying Principles

Cited by 64 publications

References 65 publications

Central regulation of feeding behavior during social isolation of rat: evidence for the role of endogenous CART system

Central regulation of feeding behavior during social isolation of rat: evidence for the role of endogenous CART system

Ontogeny of the cocaine‐ and amphetamine‐regulated transcript (CART) neuropeptide system in the brain of zebrafish, Danio rerio

Differential distribution and energy status–dependent regulation of the four CART neuropeptide genes in the zebrafish brain

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