Endocannabinoid signaling and food addiction D'ADDARIO, C; MICIONI DI BONAVENTURA, M. V; PUCCI, M ...
Neuroscience and biobehavioral reviews,
11/2014, Letnik:
47
Journal Article
Recenzirano
Overeating, frequently linked to an increasing incidence of overweight and obesity, has become epidemic and one of the leading global health problems. To explain the development of this eating ...behavior, new hypotheses involve the concept that many people might be addicted to food by losing control over their ability to regulate food intake. Among the different neurotransmitter networks that partake in the reward circuitry within the brain, a large body of evidence supports the involvement of the endocannabinoid system. Indeed, its dysfunctions might contribute to food addiction, by regulating appetite and food preference through central and peripheral mechanisms. Here, we review and discuss the role of endocannabinoid signaling in the reward circuitry, and the possible therapeutic exploitation of strategies based on its fine regulation.
Evidence suggests that binge eating may be caused by a unique interaction between dieting and stress. We developed a binge‐eating model in which female rats with a history of intermittent food ...restriction show binge‐like palatable food consumption after a 15‐minute exposure to the sight of the palatable food (frustration stress). The aim of the present study was to investigate the regulation of the stress neurohormone corticotropin‐releasing factor (CRF) system and of the nociceptin/orphanin FQ (N/OFQ) system genes in selective rat brain regions, using our animal model. Food restriction by itself seems to be responsible in the hypothalamus for the downregulation on messenger RNA levels of CRF‐1 receptor, N/OFQ and its receptor (NOP). For the latter, this alteration might be due to selective histone modification changes. Instead, CRF gene appears to be upregulated in the hypothalamus as well as in the ventral tegmental area only when rats are food restricted and exposed to frustration stress, and, of relevance, these changes appear to be due to a reduction in DNA methylation at gene promoters. Moreover, also CRF‐1 receptor gene resulted to be differentially regulated in these two brain regions. Epigenetic changes may be viewed as adaptive mechanisms to environmental perturbations concurring to facilitate food consumption in adverse conditions, that is, in this study, under food restriction and stressful conditions. Our data on N/OFQ and CRF signaling provide insight on the use of this binge‐eating model for the study of epigenetic modifications in controlled genetic and environmental backgrounds.
Binge eating is triggered by a unique interaction between dieting and stress. We observed that rats subjected to cycles of food restriction and then exposed to frustration stress showed binge eating. We provide data on target gene expression regulation (CRF and N/OFQ system genes) via epigenetic mechanisms, suggesting differential roles in selected brain regions. In the VTA, CRF system gene upregulation in response to stress might lead to the increase of high palatable food consumption through modulation of reward mechanisms.
Relapse to maladaptive eating habits during dieting is often provoked by stress and there is evidence for a role of ovarian hormones in stress responses and feeding. We studied the role of these ...hormones in stress-induced reinstatement of food seeking and medial prefrontal cortex (mPFC) neuronal activation in c-fos-GFP transgenic female rats, which express GFP in strongly activated neurons. Food-restricted ovariectomized or sham-operated c-fos-GFP rats were trained to lever-press for palatable food pellets. Subsequently, lever-pressing was extinguished and reinstatement of food seeking and mPFC neuronal activation was assessed after injections of the pharmacological stressor yohimbine (0.5-2 mg/kg) or pellet priming (1-4 noncontingent pellets). Estrous cycle effects on reinstatement were also assessed in wild-type rats. Yohimbine- and pellet-priming-induced reinstatement was associated with Fos and GFP induction in mPFC; both reinstatement and neuronal activation were minimally affected by ovarian hormones in both c-fos-GFP and wild-type rats. c-fos-GFP transgenic rats were then used to assess glutamatergic synaptic alterations within activated GFP-positive and nonactivated GFP-negative mPFC neurons following yohimbine-induced reinstatement of food seeking. This reinstatement was associated with reduced AMPA receptor/NMDA receptor current ratios and increased paired-pulse facilitation in activated GFP-positive but not GFP-negative neurons. While ovarian hormones do not appear to play a role in stress-induced relapse of food seeking in our rat model, this reinstatement was associated with unique synaptic alterations in strongly activated mPFC neurons. Our paper introduces the c-fos-GFP transgenic rat as a new tool to study unique synaptic changes in activated neurons during behavior.
Highlights • Nociceptin/orphanin FQ (N/OFQ) has been proposed as a functional antagonist of corticotropin-releasing factor (CRF). • Antagonism between N/OFQ and CRF in anxiety conditions and changes ...in the central 5-HTergic system were studied. • N/OFQ displayed anxiolytic-like effects and, administered before CRF, counteracted anxiogenic-like effects evoked by CRF. • Either N/OFQ or CRF changed central 5-HTergic system parameters: their combination annulled the single drug’s effects. • The study shows that N/OFQ may be functional antagonist of CRF anxiogenic-like effects via central 5-HT system modulation.
Cannabidiol (CBD) is the most abundant non-psychoactive component of cannabis; it displays a very low affinity for cannabinoid receptors, facilitates endocannabinoid signaling by inhibiting the ...hydrolysis of anandamide, and stimulates both transient receptor potential vanilloid 1 and 2 and serotonin type 1A receptors. Since CBD interacts with a wide variety of molecular targets in the brain, its therapeutic potential has been investigated in a number of neuropsychiatric diseases, including anxiety and mood disorders. Specifically, CBD has received growing attention due to its anxiolytic and antidepressant properties. As a consequence, and given its safety profile, CBD is considered a promising new agent in the treatment of anxiety and mood disorders. However, the exact molecular mechanism of action of CBD still remains unknown. In the present preclinical review, we provide a summary of animal-based studies that support the use of CBD as an anxiolytic- and antidepressant-like compound. Next, we describe neuropharmacological evidence that links the molecular pharmacology of CBD to its behavioral effects. Finally, by taking into consideration the effects of CBD on DNA methylation, histone modifications, and microRNAs, we elaborate on the putative role of epigenetic mechanisms in mediating CBD's therapeutic outcomes.
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