neuropeptide-y and anandamide

Topics: Amygdala; Animals; Arachidonic Acids; Arousal; Basolateral Nuclear Complex; Behavior, Animal; Benzamides; Carbamates; Depression; Disease Models, Animal; Endocannabinoids; Extinction, Psychological; Neuropeptide Y; Polyunsaturated Alkamides; Rats; Receptor, Cannabinoid, CB1; Receptors, Neuropeptide Y; Reflex, Startle; Social Behavior; Stress Disorders, Post-Traumatic

The function of small intestinal monoacylglycerol lipase (MGL) is unknown. Its expression in this tissue is surprising because one of the primary functions of the small intestine is to convert diet-derived MGs to triacylglycerol (TG), and not to degrade them. To elucidate the function of intestinal MGL, we generated transgenic mice that over-express MGL specifically in small intestine (iMGL mice). After only 3 weeks of high fat feeding, iMGL mice showed an obese phenotype; body weight gain and body fat mass were markedly higher in iMGL mice, along with increased hepatic and plasma TG levels compared to wild type littermates. The iMGL mice were hyperphagic and displayed reduced energy expenditure despite unchanged lean body mass, suggesting that the increased adiposity was due to both increased caloric intake and systemic effects resulting in a hypometabolic rate. The presence of the transgene resulted in lower levels of most MG species in intestinal mucosa, including the endocannabinoid 2-arachidonoyl glycerol (2-AG). The results therefore suggest a role for intestinal MGL, and intestinal 2-AG and perhaps other MG species, in whole body energy balance via regulation of food intake as well as metabolic rate.

Topics: Adiposity; Agouti-Related Protein; Animals; Appetite; Arachidonic Acids; Basal Metabolism; Brain; Eating; Endocannabinoids; Energy Metabolism; Glycerides; Intestine, Small; Mice; Mice, Transgenic; Monoacylglycerol Lipases; Neuropeptide Y; Obesity; Polyunsaturated Alkamides; Pro-Opiomelanocortin; Receptor, Cannabinoid, CB1; Triglycerides

The endocannabinoid system is a major regulator of food intake in many animal species. Studies conducted so far have mostly focused on mammals, and, therefore, in this study, the role of the endocannabinoid system in food intake in the sea bream Sparus aurata was investigated. The effect of different doses of the endocannabinoid anandamide (AEA), administered via water, was evaluated after different exposure times (30, 60 and 120 min) at both physiological and molecular levels. The results obtained indicate that fish exposed to AEA via water present approximately 1000-fold higher levels of AEA in both the brain and liver, which correlated with a significant increase in food intake and with the elevation of cannabinoid receptor 1 (CB(1)) and neuropeptide Y (NPY) mRNA levels in the brain. A peripheral effect of AEA was also observed, since a time-dependent increase in hepatic CB(1) mRNA and protein levels was detected. These effects were attenuated by the administration, again via water, of a selective cannabinoid CB(1) receptor antagonist (AM251). These findings indicate that the endocannabinoid AEA, at doses that stimulate food intake in fish, concomitantly stimulates the expression of the orexigenic peptide NPY as well that of its own receptor, thereby potentially enhancing its effect on food consumption. In agreement with a role of AEA in food intake in S. aurata, we found increased brain levels of both this and the other endocannabinoid, 2-arachidonoylglycerol (2-AG), following food deprivation.

Topics: Animals; Arachidonic Acids; Brain Chemistry; Cannabinoid Receptor Modulators; Eating; Endocannabinoids; Food Deprivation; Glycerides; Liver; Neuropeptide Y; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Receptor, Cannabinoid, CB1; RNA, Messenger; Sea Bream; Water

There is strong evidence that blocking CB1 receptors may reduce alcohol intake in alcohol-dependent individuals. However, there is still limited evidence that CB1 receptor antagonists may also be beneficial in the attenuation of alcohol withdrawal syndrome, even though alcohol withdrawal appears to be milder in CB1 receptor knockout mice. Here we have examined whether the CB1 receptor antagonist rimonabant (SR141716) can alleviate the behavioral symptoms and revert the neurochemical imbalance elicited by a 3-h interruption of chronic alcohol exposure (7.2% in the drinking water for 10 days) in male Wistar rats. Administration of rimonabant attenuated the strong anxiogenic traits of the animals that developed when regular alcohol intake was interrupted. This may reflect the correction of the GABA/glutamate imbalances developed by the animals that received rimonabant in various brain regions involved in emotional (e.g. prefrontal cortex) and motor (e.g. caudate-putamen and globus pallidus) responses. In addition, rimonabant also affected the dopamine deficits generated by alcohol abstinence in the amygdala and ventral-tegmental area, albeit to a lesser extent. However, this antagonist was unable to correct the impairment caused by alcohol abstinence in serotonin and neuropeptide Y. The endocannabinoid activity in the brain of alcohol-abstinent rats indicated that the behavioral and neurochemical improvements caused by rimonabant were not related to the attenuation of a possible increase in this activity generated by alcohol withdrawal. Conversely, the density of CB1 receptors was reduced in alcohol-abstinent animals (e.g. globus pallidus, substantia nigra), as were the levels of endocannabinoids and related N-acylethanolamines (e.g. amygdala, caudate-putamen). Thus, rimonabant possibly enhances an endogenous response generated by interrupting the regular use of alcohol. In summary, rimonabant might attenuate withdrawal symptoms associated with alcohol abstinence, an effect that was presumably due to the normalization of GABA and glutamate, and to a lesser extent, dopamine transmission in emotion- and motor-related areas.

Topics: Animals; Anxiety; Appetite; Arachidonic Acids; Autoradiography; Benzoxazines; Brain Chemistry; Cannabinoid Receptor Modulators; Central Nervous System Depressants; Chromatography, High Pressure Liquid; Emotions; Endocannabinoids; Enkephalins; Ethanol; Ethanolamines; Glycerides; In Situ Hybridization; Male; Morpholines; Motor Activity; Naphthalenes; Neuropeptide Y; Neurotransmitter Agents; Piperidines; Polyunsaturated Alkamides; Protein Precursors; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Rimonabant; RNA, Messenger; Stress, Psychological; Substance Withdrawal Syndrome

Little is known about the mechanism of action behind the orexigenic activity of cannabinoids. Neuropeptide Y (NPY) is one of the most potent orexigenic factors and is a key mediator in the hypothalamic control of food intake. We examined the effect of cannabinoids on NPY release using a rat hypothalamic explant model. The cannabinoid agonists anandamide (AEA) and CP55,940 both significantly augmented resting and KCl-evoked NPY release. AM251, a cannabinoid receptor antagonist, blocked the augmentation of NPY release elicited by AEA and CP55,940. Additionally, AM251 administered alone, in the absence of exogenous cannabinoid agonists, inhibited NPY release demonstrating the role of endogenous cannabinoids in NPY release. Combined, these findings demonstrate that cannabinoids augment NPY release in the hypothalamus and that this may be a potential mechanism behind the orexigenic activity of cannabinoids.

Topics: Analgesics; Animals; Arachidonic Acids; Cannabinoid Receptor Agonists; Cannabinoid Receptor Antagonists; Cannabinoids; Cyclohexanols; Dose-Response Relationship, Drug; Endocannabinoids; Hypothalamus; Male; Neuropeptide Y; Organ Culture Techniques; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Rats; Rats, Sprague-Dawley