Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice.
This investigation reports the possible role of the endocannabinoid anandamide on modulating the behavioral and neurochemical consequences of semi-starvation. We studied the effect of very low dose anandamide (0.001 mg/kg) administration on food intake, cognitive function and catecholaminergic and serotonergic pathways in two murine brain areas concerned with appetite (hypothalamus) and learning (hippocampus), and the peripheral corticosterone response to the stress of 40% diet restriction. Anandamide-treated mice consumed 44% more food (P<0.05) during 1 week of 2.5-h feeding each day. In the hypothalamus, there were significantly increased concentrations of norepinephrine (P<0.01), dopamine (P<0.05) and 5-hydroxytryptamine (5-HT) (P<0.001). In the hippocampus, anandamide increased significantly norepinephrine and dopamine, but decreased 5-HT (all at P<0.001). Diet restriction was accompanied in both areas by a significant decrease in all neurotransmitter concentrations that were partially restored by anandamide for dopamine and 5-HT, but not for norepinephrine. In animals on diet restriction, anandamide significantly improved impaired maze performance. Norepinephrine turnover and plasma corticosterone levels were also raised significantly by anandamide. The fact that low dose anandamide improved food intake, cognitive function and reversed some of the neurotransmitter changes caused by diet restriction, might have implications for the treatment of cachexia associated with acquired immunodeficiency syndrome (AIDS) and cancer, for mood changes sometimes associated with dieting, and in the extreme case, of patients with anorexia.
Hao
S
S
Department of Human Nutrition and Metabolism, The Hebrew University-Hadassah Medical School, POB 12272, Jerusalem, Israel.
Avraham
Y
Y
Mechoulam
R
R
Berry
E M
EM
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators; D002395:Catecholamines / Q000378:metabolism; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D063388:Endocannabinoids; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018377:Neurotransmitter Agents / Q000378:metabolism*; D053284:Polyunsaturated Alkamides; D011597:Psychomotor Performance / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002395:Catecholamines; D063388:Endocannabinoids; D018377:Neurotransmitter Agents; D053284:Polyunsaturated Alkamides; D012701:Serotonin; C078814:anandamide; D003345:Corticosterone