Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats

Abstract

This investigation reports the possible role of the endocannabinoid anandamide in modulating appetitive behaviour. Given that cannabinoids have been used clinically to stimulate appetite in HIV and cancer chemotherapy patients, there has been a renewed interest in the involvement of cannabinoids in appetite modulation. This is the ®rst report on the administration of anandamide into the ventromedial hypothalamus. Pre-satiated rats received an intrahypothalamic injection of anandamide (50 ng 0.5 ml 71 ) followed by measurement of food intake at 3 h post injection. Administration of anandamide induced signi®cant hyperphagia. Pretreatment with the selective CB 1 cannabinoid antagonist SR 141716 (30 mg 0.5 ml 71 ), 30 min prior to anandamide injection resulted in an attenuation of the anandamide-induced hyperphagia (P50.001). This study demonstrates that intrahypothalamic anandamide initiates appetite by stimulation of CB 1 receptors, thus providing evidence on the involvement of hypothalamic endocannabinoids in appetite initiation.

The Novel Cannabinoid CB1 Receptor Neutral Antagonist AM4113 Suppresses Food Intake and Food-Reinforced Behavior but Does not Induce Signs of Nausea in Rats

“…SR141716 attenuated the hyperphagia induced by CB1 agonists (Jamshidi and Taylor, 2001;Kirkham et al, 2002;Williams and Kirkham, 1999), and when administered alone it reduced food intake in a number of different animal models (Arnone et al, 1997;Colombo et al, 1998;Simiand et al, 1998;Williams and Kirkham, 1999). Feeding suppression induced by CB1 antagonists/inverse agonists has been demonstrated in both satiated and food-deprived animals following systemic or central administration, and after either acute or chronic treatment (Chen et al, 2004;Colombo et al, 1998;Shearman et al, 2003;Wiley et al, 2005).…”

Blood Levels of the Endocannabinoid Anandamide are Increased in Anorexia Nervosa and in Binge-Eating Disorder, but not in Bulimia Nervosa

“…Our findings show that changes in AEA levels do not seem to be related to psychopathological variables such as anxiety, depression or eating-related symptoms or duration of the illness, since no statistically significant correlations emerged between these variables and the plasma concentrations of the endocannabinoid. Since AEA has a stimulatory action on food intake (Williams and Kirkham, 1999;Hao et al, 2000;Jamshidi and Taylor, 2001), a possibility might be that the enhanced levels of the endocannabinoid in restricting anorexics may represent an adaptive response aiming at counteracting their restrictive behavior by increasing the drive to eat. However, this attempt has apparently no success in these patients, likely because psychological factors overwhelm biological mechanisms regulating eating behavior.…”

Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions

“…30 There is only one report suggesting that central administration of rimonabant or endocannabinoids through intracerebroventricular (icv) injection did not affect food intake. 31 In contrast, it has been shown in independent studies that direct injection of agonists into brain can stimulate food intake, 32,33 and icv administration of rimonabant does reduce food intake and body weight. 34 Based on the totality of these reports, it seems to be that the negative result of Gomez et al 31 may represent a special limitation of the study.…”