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Chronic adolescent exposure to Δ-9-tetrahydrocannabinol in COMT mutant mice: impact on psychosis-related and other phenotypes.
Neuropsychopharmacology. 2010 Oct; 35(11):2262-73.N

Abstract

Cannabis use confers a two-fold increase in the risk for psychosis, with adolescent use conferring even greater risk. A high-low activity catechol-O-methyltransferase (COMT) polymorphism may modulate the effects of adolescent Δ-9-tetrahydrocannabinol (THC) exposure on the risk for adult psychosis. Mice with knockout of the COMT gene were treated chronically with THC (4.0 and 8.0 mg/kg over 20 days) during either adolescence (postnatal days (PDs) 32-52) or adulthood (PDs 70-90). The effects of THC exposure were then assessed in adulthood across behavioral phenotypes relevant for psychosis: exploratory activity, spatial working memory (spontaneous and delayed alternation), object recognition memory, social interaction (sociability and social novelty preference), and anxiety (elevated plus maze). Adolescent THC administration induced a larger increase in exploratory activity, greater impairment in spatial working memory, and a stronger anti-anxiety effect in COMT knockouts than in wild types, primarily among males. No such effects of selective adolescent THC administration were evident for other behaviors. Both object recognition memory and social novelty preference were disrupted by either adolescent or adult THC administration, independent of genotype. The COMT genotype exerts specific modulation of responsivity to chronic THC administration during adolescence in terms of exploratory activity, spatial working memory, and anxiety. These findings illuminate the interaction between genes and adverse environmental exposures over a particular stage of development in the expression of the psychosis phenotype.

Authors+Show Affiliations

Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland. cotuathaigh@rcsi.ieNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20631688

Citation

O'Tuathaigh, Colm M P., et al. "Chronic Adolescent Exposure to Δ-9-tetrahydrocannabinol in COMT Mutant Mice: Impact On Psychosis-related and Other Phenotypes." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 35, no. 11, 2010, pp. 2262-73.
O'Tuathaigh CM, Hryniewiecka M, Behan A, et al. Chronic adolescent exposure to Δ-9-tetrahydrocannabinol in COMT mutant mice: impact on psychosis-related and other phenotypes. Neuropsychopharmacology. 2010;35(11):2262-73.
O'Tuathaigh, C. M., Hryniewiecka, M., Behan, A., Tighe, O., Coughlan, C., Desbonnet, L., Cannon, M., Karayiorgou, M., Gogos, J. A., Cotter, D. R., & Waddington, J. L. (2010). Chronic adolescent exposure to Δ-9-tetrahydrocannabinol in COMT mutant mice: impact on psychosis-related and other phenotypes. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 35(11), 2262-73. https://doi.org/10.1038/npp.2010.100
O'Tuathaigh CM, et al. Chronic Adolescent Exposure to Δ-9-tetrahydrocannabinol in COMT Mutant Mice: Impact On Psychosis-related and Other Phenotypes. Neuropsychopharmacology. 2010;35(11):2262-73. PubMed PMID: 20631688.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic adolescent exposure to Δ-9-tetrahydrocannabinol in COMT mutant mice: impact on psychosis-related and other phenotypes. AU - O'Tuathaigh,Colm M P, AU - Hryniewiecka,Magdalena, AU - Behan,Aine, AU - Tighe,Orna, AU - Coughlan,Catherine, AU - Desbonnet,Lieve, AU - Cannon,Mary, AU - Karayiorgou,Maria, AU - Gogos,Joseph A, AU - Cotter,David R, AU - Waddington,John L, Y1 - 2010/07/14/ PY - 2010/7/16/entrez PY - 2010/7/16/pubmed PY - 2011/8/9/medline SP - 2262 EP - 73 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 35 IS - 11 N2 - Cannabis use confers a two-fold increase in the risk for psychosis, with adolescent use conferring even greater risk. A high-low activity catechol-O-methyltransferase (COMT) polymorphism may modulate the effects of adolescent Δ-9-tetrahydrocannabinol (THC) exposure on the risk for adult psychosis. Mice with knockout of the COMT gene were treated chronically with THC (4.0 and 8.0 mg/kg over 20 days) during either adolescence (postnatal days (PDs) 32-52) or adulthood (PDs 70-90). The effects of THC exposure were then assessed in adulthood across behavioral phenotypes relevant for psychosis: exploratory activity, spatial working memory (spontaneous and delayed alternation), object recognition memory, social interaction (sociability and social novelty preference), and anxiety (elevated plus maze). Adolescent THC administration induced a larger increase in exploratory activity, greater impairment in spatial working memory, and a stronger anti-anxiety effect in COMT knockouts than in wild types, primarily among males. No such effects of selective adolescent THC administration were evident for other behaviors. Both object recognition memory and social novelty preference were disrupted by either adolescent or adult THC administration, independent of genotype. The COMT genotype exerts specific modulation of responsivity to chronic THC administration during adolescence in terms of exploratory activity, spatial working memory, and anxiety. These findings illuminate the interaction between genes and adverse environmental exposures over a particular stage of development in the expression of the psychosis phenotype. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/20631688/Chronic_adolescent_exposure_to_Δ_9_tetrahydrocannabinol_in_COMT_mutant_mice:_impact_on_psychosis_related_and_other_phenotypes_ L2 - http://dx.doi.org/10.1038/npp.2010.100 DB - PRIME DP - Unbound Medicine ER -