Chronic adolescent exposure to Δ-9-tetrahydrocannabinol in COMT mutant mice: impact on psychosis-related and other phenotypes.
Colm M P O'Tuathaigh, Magdalena Hryniewiecka, Aine Behan, Orna Tighe, Catherine Coughlan, Lieve Desbonnet, Mary Cannon, Maria Karayiorgou, Joseph A Gogos, David R Cotter, John L. Waddington
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology October 2010 DOI: 10.1038/npp.2010.100 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Mice (COMT knockout and wild-type) |
| Dose | 4.0 and 8.0 mg/kg over 20 days |
| Duration | 20 days of THC exposure during adolescence (postnatal days 32-52) or adulthood (postnatal days 70-90), with behavioral assessment in adulthood |
| Measures | exploratory activity, spontaneous and delayed alternation, object recognition memory, sociability and social novelty preference, elevated plus maze |
| Topics | Cannabis |
| Key findings | Adolescent THC administration increased exploratory activity, impaired spatial working memory, and reduced anxiety more strongly in COMT knockout mice than in wild types, mainly in males. Object recognition memory and social novelty preference were disrupted by THC regardless of genotype. |
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.