NDLI: Distinct Neurobehavioural Effects of Cannabidiol in Transmembrane Domain Neuregulin 1 Mutant Mice

Content Provider	PubMed Central
Author	Long, Leonora E. Chesworth, Rose Huang, Xu-feng Wong, Alexander Spiro, Adena Mcgregor, Iain S. Arnold, Jonathon C. Karl, Tim
Editor	Hashimoto, Kenji
Copyright Year	2012
Abstract	The cannabis constituent cannabidiol (CBD) possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET) mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT) received vehicle or CBD (1, 50 or 100 mg/kg i.p.) for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 HET mice displayed locomotor hyperactivity, PPI deficits and reduced 5-HT2A receptor binding density in the substantia nigra, but these phenotypes were not reversed by CBD. However, long-term CBD (50 and 100 mg/kg) selectively enhanced social interaction in Nrg1 TM HET mice. Furthermore, acute CBD (100 mg/kg) selectively increased PPI in Nrg1 TM HET mice, although tolerance to this effect was manifest upon repeated CBD administration. Long-term CBD (50 mg/kg) also selectively increased GABAA receptor binding in the granular retrosplenial cortex in Nrg1 TM HET mice and reduced 5-HT2A binding in the substantia nigra in WT mice. Nrg1 appears necessary for CBD-induced anxiolysis since only WT mice developed decreased anxiety-related behaviour with repeated CBD treatment. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD, which does not reverse the schizophrenia-relevant phenotypes.
Related Links	http://dx.doi.org/10.1371/journal.pone.0034129
Starting Page	34129
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	4
Volume Number	7
Language	English
Publisher	Public Library of Science
Publisher Date	2012-04-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Neuregulin 1 Improves Glucose Tolerance in db/db Mice

Transmembrane and Ubiquitin-Like Domain Containing 1 (Tmub1) Regulates Locomotor Activity and Wakefulness in Mice and Interacts with CAMLG

Neuregulin 1 Expression and Electrophysiological Abnormalities in the Neuregulin 1 Transmembrane Domain Heterozygous Mutant Mouse

Subchronic Peripheral Neuregulin-1 Increases Ventral Hippocampal Neurogenesis and Induces Antidepressant-Like Effects

Transmembrane and Coiled-Coil Domain Family 1 Is a Novel Protein of the Endoplasmic Reticulum

Distinct Phyllosphere Bacterial Communities on Arabidopsis Wax Mutant Leaves

Aging Kit Mutant Mice Develop Cardiomyopathy

Frontal Bone Insufficiency in Gsk3β Mutant Mice

Protective Effects of Cannabidiol on Lesion-Induced Intervertebral Disc Degeneration

Distinct Neurobehavioural Effects of Cannabidiol in Transmembrane Domain Neuregulin 1 Mutant Mice

Similar Documents

Neuregulin 1 Improves Glucose Tolerance in db/db Mice

Transmembrane and Ubiquitin-Like Domain Containing 1 (Tmub1) Regulates Locomotor Activity and Wakefulness in Mice and Interacts with CAMLG

Neuregulin 1 Expression and Electrophysiological Abnormalities in the Neuregulin 1 Transmembrane Domain Heterozygous Mutant Mouse

Subchronic Peripheral Neuregulin-1 Increases Ventral Hippocampal Neurogenesis and Induces Antidepressant-Like Effects

Transmembrane and Coiled-Coil Domain Family 1 Is a Novel Protein of the Endoplasmic Reticulum

Distinct Phyllosphere Bacterial Communities on Arabidopsis Wax Mutant Leaves

Aging Kit Mutant Mice Develop Cardiomyopathy

Frontal Bone Insufficiency in Gsk3β Mutant Mice

Protective Effects of Cannabidiol on Lesion-Induced Intervertebral Disc Degeneration

Distinct Neurobehavioural Effects of Cannabidiol in Transmembrane Domain Neuregulin 1 Mutant Mice