Regulatory peptides
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Regulatory peptides · Mar 2013
Tolerance to hypophagia induced by prolonged treatment with a CB1 antagonist is related to the reversion of anorexigenic neuropeptide gene expression in the hypothalamus.
It is well established that treatment with rimonabant, a CB1 antagonist, decreases food intake and body weight gain. In part, these responses are mediated by increased activity of hypothalamic neurons related with energy homeostasis. However, food consumption is reversed to basal level during prolonged CB1 antagonist treatment, suggesting tolerance to its anorexigenic effect. ⋯ There was an increase in CB1 mRNA expression in the PVN of rats that received both acute and prolonged-rimonabant treatment. Interestingly, rats subjected to prolonged rimonabant treatment had no changes in food intake, body weight gain, hypothalamic mRNA expression, Fos expression and CRF and CART neuron activation. These data indicate that tolerance to hypophagic effects of CB1 antagonist, rimonabant, is associated with reversion of hypothalamic neuropeptide gene expression related to regulation of energy homeostasis.