Enhancement of endocannabinoid signalling during adolescence: Modulation of impulsivity and long-term consequences on metabolic brain parameters in early maternally deprived rats.
Pharmacological modulation of the endocannabinoid system is a novel but poorly explored field for potential therapy. Early maternal deprivation represents an animal model for specific aspects of neuropsychiatric disorders. This study explored whether a pharmacological manipulation of the endocannabinoid system at adolescence may restore altered phenotypes resulting from early maternal deprivation. Wistar male rats, maternally deprived for 24 h on postnatal day (PND) 9, were administered the fatty-acid amide hydrolase (FAAH) inhibitor URB597 (0, 0.1 or 0.5 mg/kg/day) for six days during adolescence (PND 31-43), while tested in the intolerance-to-delay task. Deprived (DEP) adolescent rats showed a trend for higher impulsivity levels and an increased locomotor response to novelty when compared to non-deprived (NDEP) controls. The low dose of URB597 effectively decreased impulsive behaviour specifically in DEP subjects. Moreover, long-term metabolic brain changes, induced by drug treatment during adolescence, were detected in DEP animals using proton magnetic resonance spectroscopy ((1)H MRS). Significant changes were only found within the hippocampus: N-acetyl-aspartate and total creatine were up-regulated by the low dose; glutamate and glutamate plus glutamine were conversely down-regulated by the higher dose. In summary, administration of URB597 during adolescence increased self-control behaviour and produced enduring brain biochemical modifications, in a model for neuropsychiatric disorders.
Marco
Eva María
EM
Unit of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Roma, Italy.
Adriani
Walter
W
Canese
Rossella
R
Podo
Franca
F
Viveros
Maria Paz
MP
Laviola
Giovanni
G
D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001921:Brain / Q000254:growth & development*; D001923:Brain Chemistry / Q000502:physiology*; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002219:Carbamates / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007175:Impulsive Behavior / Q000523:psychology*; D009682:Magnetic Resonance Spectroscopy; D008426:Maternal Deprivation; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D015430:Weight Gain / Q000187:drug effects; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001549:Benzamides; D063385:Cannabinoid Receptor Modulators; D002219:Carbamates; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester