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Enhancement of endocannabinoid signalling during adolescence: Modulation of impulsivity and long-term consequences on metabolic brain parameters in early maternally deprived rats.
- Source :
-
Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2007 Feb; Vol. 86 (2), pp. 334-45. Date of Electronic Publication: 2006 Nov 13. - Publication Year :
- 2007
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Abstract
- 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.
- Subjects :
- Amidohydrolases antagonists & inhibitors
Animals
Benzamides pharmacology
Carbamates pharmacology
Conditioning, Operant drug effects
Enzyme Inhibitors pharmacology
Female
Hippocampus drug effects
Hippocampus metabolism
Hippocampus physiology
Magnetic Resonance Spectroscopy
Motor Activity drug effects
Neostriatum drug effects
Neostriatum metabolism
Nucleus Accumbens drug effects
Nucleus Accumbens metabolism
Pregnancy
Rats
Rats, Wistar
Weight Gain drug effects
Brain growth & development
Brain Chemistry physiology
Cannabinoid Receptor Modulators physiology
Endocannabinoids
Impulsive Behavior psychology
Maternal Deprivation
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0091-3057
- Volume :
- 86
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Pharmacology, biochemistry, and behavior
- Publication Type :
- Academic Journal
- Accession number :
- 17101171
- Full Text :
- https://doi.org/10.1016/j.pbb.2006.10.006