Home > Chronic adolescent exposure to Delta-9-Tetrahydrocannabinol in COMT mutant mice: impact on indices of dopaminergic, endocannabinoid and GABAergic pathways.

Behan, Aine and Hryniewiecka, Magdalena and O'Tuathaigh, Colm MP and Kinsella, Anthony and Cannon, Mary and Karayiorgou, Maria and Gagos, Joseph A and Waddington, John L and Cotter, David R (2012) Chronic adolescent exposure to Delta-9-Tetrahydrocannabinol in COMT mutant mice: impact on indices of dopaminergic, endocannabinoid and GABAergic pathways. Neuropsychopharmacology , 37 , pp. 1773-1783.

URL: http://www.nature.com/npp/journal/vaop/ncurrent/fu...

Cannabis use confers a two-fold increase in risk for psychosis, with adolescent use conferring an even greater risk. A high-low activity polymorphism in catechol-O-methyltransferase (COMT), a gene encoding the COMT enzyme involved in dopamine clearance in the brain, may interact with adolescent cannabis exposure to increase risk for schizophrenia.

The impact of such an interaction on central neurotransmitter pathways implicated in schizophrenia is unknown. Male mice with knockout of the COMT gene were treated chronically with delta-9-tetrahydrocannabinol (THC) during adolescence (postnatal day 32–52). We measured the size and density of GABAergic cells and the protein expression of cannabinoid receptor 1 (CB1R) in the prefrontal cortex (PFC) and hippocampus (HPC) in knockout mice relative to heterozygous mutants and wild-type controls. Size and density of dopaminergic neurons was also assessed in the ventral tegmental area (VTA) across the genotypes. COMT genotype × THC treatment interactions were observed for: (1) dopaminergic cell size in the VTA, (2) CB1R protein expression in the HPC, and (3) parvalbumin (PV) cell size in the PFC. No effects of adolescent THC treatment were observed for PV and dopaminergic cell density across the COMT genotypes. COMT genotype modulates the effects of chronic THC administration during adolescence on indices of neurotransmitter function in the brain. These findings illuminate how COMT deletion and adolescent cannabis use can interact to modulate the function of neurotransmitters systems implicated in schizophrenia.

 

Item Type:Article
Date:2012
Page Range:pp. 1773-1783
Volume:37
EndNote:View
Accession Number:HRB (Not in collection)
Subjects:A Substance use, abuse, and dependence > Effects and consequences
B Substances > Cannabis / Marijuana
B Substances > New (novel) psychoactive substances > Gabapentinoids GABA (Pregabalin / Gabapentin)
G Health and disease > State of health > Mental health
G Health and disease > Substance related disorder > Substance related mental disorder
T Demographic characteristics > Adolescent / youth (teenager / young person)
VA Geographic area > Europe > Ireland

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