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 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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 13
- Cannabis Use during Adolescent Development: Susceptibility to Psychiatric Illness Frontiers in Psychiatry 2013
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions Neuropsychopharmacology August 22, 2022
- THC and CBD: Villain versus Hero? Insights into Adolescent Exposure. International Journal of Molecular Sciences March 9, 2023
- Psychotropic Effects of Cannabis Plant-Based Therapeutics, Volume 1 2023
and 8 more in the library
Cites 13
- Causal association between cannabis and psychosis: examination of the evidence The British Journal of Psychiatry January 30, 2004
- The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychological Medicine October 2009
- Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus August 2009
- Cannabis and psychosis/schizophrenia: human studies European Archives of Psychiatry and Clinical Neuroscience July 16, 2009
- Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology February 2009
and 8 more in the library