Genetic dissection of behavioural and autonomic effects of Delta(9)-tetrahydrocannabinol in mice.
Krisztina Monory, Heike Blaudzun, Federico Massa, Nadine Kaiser, Thomas Lemberger, Günther Schütz, Carsten T. Wotjak, Beat Lutz, Giovanni Marsicano
PLoS Biology October 2007 DOI: 10.1371/journal.pbio.0050269 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study using conditional knockout mouse lines Peer reviewed |
|---|---|
| Population | Conditional knockout mouse lines lacking CB1 in specific neuronal subpopulations, compared with wild-type littermates |
| Intervention | Delta(9)-tetrahydrocannabinol (THC) |
| Topics | Cannabis |
| Key points | Mice lacking CB1 in GABAergic neurons responded to THC similarly to wild-type littermates, whereas deletion of CB1 in all principal neurons abolished or strongly reduced behavioral and autonomic responses. Locomotor and hypothermic effects depended on cortical glutamatergic neurons, while the cataleptic effect was blocked by deletion of CB1 from most striatal neurons and a subpopulation of cortical glutamatergic neurons. |
Abstract
Marijuana and its main psychotropic ingredient Delta(9)-tetrahydrocannabinol (THC) exert a plethora of psychoactive effects through the activation of the neuronal cannabinoid receptor type 1 (CB1), which is expressed by different neuronal subpopulations in the central nervous system. The exact neuroanatomical substrates underlying each effect of THC are, however, not known. We tested locomotor, hypothermic, analgesic, and cataleptic effects of THC in conditional knockout mouse lines, which lack the expression of CB1 in different neuronal subpopulations, including principal brain neurons, GABAergic neurons (those that release gamma aminobutyric acid), cortical glutamatergic neurons, and neurons expressing the dopamine receptor D1, respectively. Surprisingly, mice lacking CB1 in GABAergic neurons responded to THC similarly as wild-type littermates did, whereas deletion of the receptor in all principal neurons abolished or strongly reduced the behavioural and autonomic responses to the drug. Moreover, locomotor and hypothermic effects of THC depend on cortical glutamatergic neurons, whereas the deletion of CB1 from the majority of striatal neurons and a subpopulation of cortical glutamatergic neurons blocked the cataleptic effect of the drug. These data show that several important pharmacological actions of THC do not depend on functional expression of CB1 on GABAergic interneurons, but on other neuronal populations, and pave the way to a refined interpretation of the pharmacological effects of cannabinoids on neuronal functions.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 15
- Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors PLoS Biology July 9, 2015
- Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Neuropsychopharmacology January 26, 2020
- Effects of Δ9-THC and Type-1 Cannabinoid Receptor Agonists in the Elevated Plus Maze Test of Anxiety: A Systematic Review and Meta-Analysis. Cannabis and Cannabinoid Research February 2023
- THC and CBD: Similarities and differences between siblings. Neuron February 1, 2023
- Highway to hell or magic smoke? The dose-dependence of Δ9-THC in place conditioning paradigms. Learning & Memory September 2018
and 10 more in the library
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