Background and purpose: Evidence indicates that the endocannabinoid, 2-arachidonoylglycerol (2-AG), increases food intake when injected into the nucleus accumbens shell (NAcS), thereby potentially activating hypothalamic nuclei involved in food intake regulation. We aimed to evaluate potential orexigenic effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide hydrolase (FAAH) inhibitor, and OMDM-1, an inhibitor of anandamide uptake, injected in the NAcS, as well as the effect of these treatments on activation of hypothalamic nuclei. Experimental approach: Drugs were given into the NAcS of rats and food intake quantified during the next 4 h. In other groups, after the same treatments the brains were processed for c-Fos immunohistochemistry with focus on hypothalamic nuclei. Additional groups were used to quantify endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT and OMDM-1 intra-NAcS injections. Key results. Our results indicate that the above treatments stimulate food intake during 4 h post-injection. They also increase c-Fos immunoreactivity in hypothalamic nuclei. The CB 1 antagonist, AM251, blocked these effects. Finally, we found elevated levels of 2-AG, but not anandamide, after intra-NAcS injections of AA5HT. Conclusions and implications: These data support the involvement of the endocannabinoid system in feeding behavior at the level of the NAcS and hypothalamus. In addition, this is the first experimental demonstration that the pharmacological inhibition of endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that the endocannabinoid degrading proteins can be a target for treating eating disorders.
Anandamide (ANA) alters sleep by increasing the amount of time spent in slow wave sleep 2 (SWS2) and rapid eye movement sleep (REMS) at the expense of wakefulness (W) in rats. In this report, we describe a similar effect of ANA when injected itracerebroventricularly (i.c.v.) or into the peduriculopontine tegmental nucleus (PPTg) and the lack of an effect when ANA is administered into the medial preoptic area (MPOA). Furthermore, the i.c.v. or PPTg administration of SR141716A, a CB1 antagonist, or U73122, a PLC inhibitor, 15 min prior to ANA, readily prevents the ANA induced changes in sleep. The present results suggest that a cannabinoid system in the PPTg may be involved in sleep regulation and that the cannabinoid effect is mediated by the CB1 receptor coupled to a PLC second messenger system.
Changes in the brain, which include changes in the endocannabinoid system, prompt it to use different strategies (spatial and procedural, or others not evaluated in this study) to cope with the environmental demands. These cerebral changes are adaptive responses to the light-dark cycle.
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