Type

Journal Article

Authors

John L Waddington
David R Cotter
Joseph A Gogos
Maria Karayiorgou
Mary Cannon
Lieve Desbonnet
Catherine Coughlan
Orna Tighe
Aine Behan
Magdalena Hryniewiecka
and 1 others

Subjects

Biochemistry

Topics
phenotype catechol o methyltransferase male mice knockout mice drug effects physiology psychotic disorders tetrahydrocannabinol age factors animals mutation female random allocation exploratory behavior genetics administration dosage enzymology

Chronic adolescent exposure to Δ-9-tetrahydrocannabinol in COMT mutant mice: impact on psychosis-related and other phenotypes. (2010)

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.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

John L Waddington, David R Cotter, Joseph A Gogos, Maria Karayiorgou, Mary Cannon, Lieve Desbonnet, Catherine Coughlan, Orna Tighe, Aine Behan, Magdalena Hryniewiecka and 1 others

Experts in our system

1
John L Waddington
Royal College of Surgeons in Ireland
Total Publications: 170
 
2
David R Cotter
Royal College of Surgeons in Ireland
Total Publications: 56
 
3
Mary Cannon
Royal College of Surgeons in Ireland
Total Publications: 90
 
4
Lieve Desbonnet
University College Cork
Total Publications: 26
 
5
Orna Tighe
Royal College of Surgeons in Ireland
Total Publications: 37