4.6 Article

Effect of cannabidiol on muscarinic neurotransmission in the pre-frontal cortex and hippocampus of the poly I:C rat model of schizophrenia

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2019.109640

Keywords

Cannabidiol; Muscarinic; Acetylcholine; Maternal immune activation; Schizophrenia; Cognition

Funding

  1. University of Wollongong Faculty of Science, Medicine and Health Advancement Grant [2015/SPGA-S/02]
  2. Centre for Medical and Molecular Biosciences
  3. Australian Government Research Training Program Scholarship from the University of Wollongong
  4. Daniel Beck Memorial Award from Neuroscience Research Australia
  5. Beck Family

Ask authors/readers for more resources

Cognitive impairment is a core symptom of schizophrenia; however, current antipsychotic drugs have limited efficacy to treat these symptoms and can cause serious side-effects, highlighting a need for novel therapeutics. Cannabidiol (CBD) is a non-intoxicating phytocannabinoid that has demonstrated pro-cognitive effects in multiple disease states, including a maternal immune activation (poly I:C) model of schizophrenia, but the mechanisms underlying the efficacy of CBD require investigation. Muscarinic neurotransmission is highly implicated in the cognitive impairments of schizophrenia; however, the effect of CBD on this system is unknown. We examined alterations in markers of muscarinic neurotransmission in the pre-frontal cortex (PFC) and hippocampus (HPC) following CBD treatment. Pregnant Sprague-Dawley rats (n = 16) were administered poly I:C (4 mg/kg) or saline. Adult offspring were treated (3-weeks) with CBD (10 mg/kg) or vehicle. Receptor autoradiography (using [H-3]pirenzepine) was used to examine changes in muscarinic M1/M4 receptor (M1/M4R) binding density. Levels of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) protein expression were examined using Western blot. M1/M4R binding density was downregulated in the PFC and CA1/CA2 and CA3 subregions in male poly I:C offspring. M1/M4R deficits were normalised after CBD treatment. ChAT protein expression was reduced in the HPC of male poly I:C offspring, while CBD treated poly I:C offspring exhibited control-like ChAT levels. AChE levels were unaltered in any of the groups. There were also no changes in muscarinic signalling in female offspring. These findings demonstrate that CBD can normalise muscarinic neurotransmission imbalances in male poly I:C offspring in regions of the brain implicated in cognition.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available