Cannabis Differentially Disrupts Neural Circuit Oscillatory Dynamics and Sensory Filtering in Rats: Implications for Schizophrenia

Abstract

Neural circuit oscillations are promising targets for investigating changes in brain connectivity underlying the association between cannabis use and schizophrenia. Reflecting the coordination of multiple neurotransmitter systems implicated in schizophrenia, aberrant neural circuit oscillatory activity often corresponds to schizophrenia-like changes in behaviour and is also observed after cannabinoid exposure. However, the relative effects of vapourized phytocannabinoids on schizophrenia-like neural circuit oscillations and cognitive processing remain unknown. The studies in this thesis aimed to extend existing preclinical evidence of aberrant neural circuit oscillations as an integral mechanism linking cannabis use and schizophrenia, by characterizing the influence of phytocannabinoid abundance on altered corticolimbic neural circuit oscillatory and sensory filtering deficits relevant to schizophrenia. In the second chapter, two within-subject studies were used to determine that isolate THC vapour exposure reduces neural circuit oscillatory power and coherence in experimentally naïve male rats and cannabis flower vapour exposure dose-dependently disrupts sensory filtering selectively for rats with reduced baseline performance. In the third chapter, two within-subject studies were used to determine that cannabis flower vapour exposure reduces oscillatory power in experimentally naïve male rats, as well as in a neurodevelopmental rat model of schizophrenia, and exposure to a cannabis flower vapour with different amounts of cannabinoids has a differential effect, without either exposure disrupting sensory filtering. Taken together, the effects of phytocannabinoid exposure on neural circuit oscillations and associated sensory filtering are highly dependent on the type, dose, and relative abundance of phytocannabinoid exposure, as well as baseline differences in cognition. Altered neural circuit oscillations may also be a biomarker for the effects of cannabis when cognitive disruptions are not evident.