Peroxisome proliferator-activated receptor-γ (PPARγ) has been reported to be involved in the etiology of pathological features of Alzheimer's disease (AD). Cannabidiol (CBD), a Cannabis derivative devoid of psychomimetic effects, has attracted much attention because of its promising neuroprotective properties in rat AD models, even though the mechanism responsible for such actions remains unknown. This study was aimed at exploring whether CBD effects could be subordinate to its activity at PPARγ, which has been recently indicated as its putative binding site. CBD actions on β-amyloid-induced neurotoxicity in rat AD models, either in presence or absence of PPAR antagonists were investigated. Results showed that the blockade of PPARγ was able to significantly blunt CBD effects on reactive gliosis and subsequently on neuronal damage. Moreover, due to its interaction at PPARγ, CBD was observed to stimulate hippocampal neurogenesis. All these findings report the inescapable role of this receptor in mediating CBD actions, here reported.

No abstract

Because of its lack of toxicity, its ability in reducing inflammation and its selective PPARα action, PEA might be an innovative molecule to broaden pharmacological strategies against UC.

Dieting to control body weight involves cycles of deprivation from palatable food that can promote compulsive eating. The present study shows that rats withdrawn from intermittent access to palatable food exhibit overeating of palatable food upon renewed access and an affective withdrawal-like state characterized by corticotropin-releasing factor-1 (CRF 1) receptor antagonistreversible behaviors, including hypophagia, motivational deficits to obtain less palatable food, and anxiogenic-like behavior. Withdrawal was accompanied by increased CRF expression and CRF 1 electrophysiological responsiveness in the central nucleus of the amygdala. We propose that recruitment of anti-reward extrahypothalamic CRF-CRF 1 systems during withdrawal from palatable food, analogous to abstinence from abused drugs, may promote compulsive selection of palatable food, undereating of healthier alternatives, and a negative emotional state when intake of palatable food is prevented.eating disorders ͉ obesity ͉ palatability ͉ palatable food dependence ͉ withdrawal F orms of obesity and eating disorders, similar to drug addiction, can be conceptualized as chronic relapsing conditions with alternating periods of abstinence (i.e., dieting to avoid ''forbidden'' palatable foods) and relapse (i.e., compulsive, often uncontrollable, eating of high-palatable foods) that continue despite negative consequences (1). Although the positive reinforcing properties of palatable foods are well known (2, 3), less attention has been given to their negative reinforcing properties (4-6), namely the increased probability of a behavioral response produced by removal of an aversive stimulus (e.g., intake of palatable food to relieve negative emotional states). Intermittent cycles of extended use of drugs of abuse can progressively lead to ''affective dependence,'' observed as a need for higher and/or more regular quantities of the drug to maintain a given emotional set point as well as a negative emotional state upon cessation of drug intake (7,8). Such affective withdrawal may maintain use and motivate relapse via the negative reinforcing properties of continuing and resuming drug use, respectively (7,8).Extrahypothalamic corticotropin-releasing factor (CRF) brain stress systems are putatively involved in the transition from drug use to dependence, during which intake of abused drugs becomes increasingly motivated by these negative, rather than positive, reinforcement mechanisms. CRF plays a motivationally relevant role in withdrawal syndromes for every major drug of abuse, including alcohol, nicotine, cocaine, opiates, amphetamines, and tetrahydrocannabinol (7,8). By analogy, repeated cycles of intermittent, extended access to highly palatable food were hypothesized to induce CRF system neuroadaptations similar to those seen in drug dependence models (4, 5, 9). ResultsIntermittent, extended access to palatable food progressively leads to undereating of less preferred diets when palatable food is not available and to overeating of palatable food upon renewed ...

Background and purpose: Pharmacological inhibition of beta-amyloid (Ab) induced reactive gliosis may represent a novel rationale to develop drugs able to blunt neuronal damage and slow the course of Alzheimer's disease (AD). Cannabidiol (CBD), the main non-psychotropic natural cannabinoid, exerts in vitro a combination of neuroprotective effects in different models of Ab neurotoxicity. The present study, performed in a mouse model of AD-related neuroinflammation, was aimed at confirming in vivo the previously reported antiinflammatory properties of CBD. Experimental approach: Mice were inoculated with human Ab (1-42) peptide into the right dorsal hippocampus, and treated daily with vehicle or CBD (2.5 or 10 mg kg À1 , i.p.) for 7 days. mRNA for glial fibrillary acidic protein (GFAP) was assessed by in situ hybridization. Protein expression of GFAP, inducible nitric oxide synthase (iNOS) and IL-1b was determined by immunofluorescence analysis. In addition, ELISA assay of IL-1b level and the measurement of NO were performed in dissected and homogenized ipsilateral hippocampi, derived from vehicle and Ab inoculated mice, in the absence or presence of CBD. Key results: In contrast to vehicle, CBD dose-dependently and significantly inhibited GFAP mRNA and protein expression in Ab injected animals. Moreover, under the same experimental conditions, CBD impaired iNOS and IL-1b protein expression, and the related NO and IL-1b release. Conclusion and implications:The results of the present study confirm in vivo anti-inflammatory actions of CBD, emphasizing the importance of this compound as a novel promising pharmacological tool capable of attenuating Ab evoked neuroinflammatory responses.