The mainstay treatment for
schizophrenia is
antipsychotic drugs (APDs), which are mostly effective against the positive symptoms (e.g.
hallucinations), but provide minimal benefits for the negative symptoms (e.g. social withdrawal) and cognitive deficits. We have recently shown that treatment with the non-intoxicating phytocannabinoid,
cannabidiol (CBD), can improve cognition and social interaction deficits in a maternal immune activation (MIA) model relevant to the aetiology of
schizophrenia, however, the mechanisms underlying this effect are unknown. An imbalance in the main excitatory (
glutamate) and inhibitory (
GABA)
neurotransmitter systems in the brain plays a role in the pathophysiology of
schizophrenia. Therefore, the
endocannabinoid system could represent a therapeutic target for
schizophrenia as a regulator of
glutamate and
GABA release via the
CB1 receptor (CB1R). This study investigated the effects of chronic CBD treatment on markers of glutamatergic, GABAergic and
endocannabinoid signalling in brain regions implicated in social behaviour and cognitive function, including the prefrontal cortex (PFC) and hippocampus (HPC). Time-mated pregnant Sprague-Dawley rats (n = 16) were administered
poly I:C (4 mg/kg, i.v.) or saline (control) on gestational day 15. Male offspring were injected with CBD (10 mg/kg, i.p.) or vehicle twice daily from postnatal day 56 for 3 weeks. The prefrontal cortex (PFC) and hippocampus (HPC) were collected for post-mortem receptor binding and Western blot analyses (n = 8 per group). CBD treatment attenuated
poly I:C-induced deficits in
cannabinoid CB1 receptor binding in the PFC and
glutamate decarboxylase 67, the
enzyme that converts
glutamate to
GABA, in the HPC. CBD treatment increased
parvalbumin levels in the HPC, regardless of whether offspring were exposed to
poly I:C in utero. Conversely, CBD did not affect
N-methyl-d-aspartate receptor and
gamma-aminobutyric acid (
GABA) A receptor binding or
protein levels of
fatty acid amide hydrolase, the
enzyme that degrades the
endocannabinoid,
anandamide. Overall, these findings show that CBD can restore
cannabinoid/GABAergic signalling deficits in regions of the brain implicated in
schizophrenia pathophysiology following maternal
poly I:C exposure. These findings provide novel evidence for the potential mechanisms underlying the
therapeutic effects of CBD treatment in the
poly I:C model.