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Involvement of hypothalamic peptides in the anorectic action of the CB1 receptor antagonist rimonabant (SR 141716)
Abstract
Numerous studies have demonstrated that administration of rimonabant (SR 141716), a CB(1) receptor antagonist, causes a decrease in energy intake. However, the mechanisms by which rimonabant exerts its anorectic actions are unclear. The main focus of the study reported here was to establish the chemical identity of neurons that may subserve the anorectic effects of rimonabant. As such three approaches were utilised: (i) the identification of rimonabant-activated neurons using Fos as a marker of neuronal activity; (ii) the identification of the chemical phenotype of rimonabant-activated neurons by combining immunocytochemical identification of Fos and feeding-related peptides; and (iii) the evaluation of the effect of rimonabant on messenger RNA (mRNA) and protein for a number of feeding-related peptides. Rimonabant-induced Fos-positive nuclei were localized within a range of discrete hypothalamic regions with a predominance in the parvocellular part of the paraventricular nucleus of the hypothalamus, dorsomedial hypothalamus, arcuate nucleus and lateral hypothalamic area. Furthermore, Fos labelling within these hypothalamic regions was colocalized with anorexigenic and orexigenic peptides including melanin-concentrating hormone (MCH), orexin, cocaine- and amphetamine-regulated transcript (CART) and alpha-melanocyte-stimulating hormone (alpha-MSH). Rimonabant specifically induced a decrease in NPY and an increase in CART and alpha-MSH mRNA and protein, consistent with its effect in reducing food intake and increasing energy expenditure. As such these data provide insights into the mechanisms of action that may underpin rimonabant's effects on energy balance and body weight.
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Intraperitoneal administration of rimonabant reduces food intake and induces neuronal activation in hypothalamic nuclei involved in food intake regulation, such as the paraventricular nucleus.
“For instance, intraperitoneal administration of rimonabant (an antagonist for the cannabinoid receptor CB 1 ) reduces food intake (Thornton-Jones et al., 2006) and induces neuronal activation in several hypothalamic nuclei involved in food intake regulation, such as the paraventricular nucleus (Verty et al., 2009).”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Verty et al., 2009
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Metadata
- Authors
- Verty, A. N. A., Boon, W. M., Mallet, P. E., McGregor, I. S., & Oldfield, B. J.
- Affiliations
- Monash University (AU)
- Wilfrid Laurier University (CA)
- The University of Sydney (AU)
- Corresponding author
- Oldfield, Brian J.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2009-06
- Volume
- 29
- Issue
- 11
- Pages
- 2207-2216
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W1965336104
- Cited by
- 39
- References
- 54
- Citations by year
- 2025: 1 · 2023: 1 · 2021: 2 · 2020: 3 · 2018: 5 · 2017: 6 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 5
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Keywords
- rimonabant, CB1 receptor antagonist, hypothalamus, FOS, paraventricular nucleus, dorsomedial hypothalamus, arcuate nucleus, lateral hypothalamus, melanin-concentrating hormone, orexin, cocaine- and amphetamine-regulated transcript, alpha-melanocyte-stimulating hormone, neuropeptide Y, energy balance, body weight regulation
- MeSH terms
- Rimonabant, Animals, Appetite Depressants, Food Deprivation, Hypothalamic Hormones, Hypothalamus, Male, Piperidines, Pyrazoles, Rats, Sprague-Dawley, Receptors, Cannabinoid, Rats, Cannabinoid Receptor Antagonists
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