Abstract
Much of our knowledge of the endocannabinoid system in schizophrenia comes from behavioral measures in rodents, like prepulse inhibition of the acoustic startle and open-field locomotion, which are commonly used along with neurochemical approaches or drug challenge designs. Such methods continue to map fundamental mechanisms of sensorimotor gating, hyperlocomotion, social interaction, and underlying monoaminergic, glutamatergic, and GABAergic disturbances. These strategies will require, however, a greater use of neurophysiological tools to better inform clinical research. In this sense, electrophysiology and viral vector-based circuit dissection, like optogenetics, can further elucidate how exogenous cannabinoids worsen (e.g., tetrahydrocannabinol, THC) or ameliorate (e.g., cannabidiol, CBD) schizophrenia symptoms, like hallucinations, delusions, and cognitive deficits. Also, recent studies point to a complex endocannabinoid-endovanilloid interplay, including the influence of anandamide (endogenous CB1 and TRPV1 agonist) on cognitive variables, such as aversive memory extinction. In fact, growing interest has been devoted to TRPV1 receptors as promising therapeutic targets. Here, these issues are reviewed with an emphasis on the neurophysiological evidence. First, we contextualize imaging and electrographic findings in humans. Then, we present a comprehensive review on rodent electrophysiology. Finally, we discuss how basic research will benefit from further combining psychopharmacological and neurophysiological tools.
Highlights
Heavy cannabis use may precipitate or exacerbate schizophrenia symptoms
Co-administration of WIN and a dopamine receptor antagonist into the medial PFC (mPFC) blocked this behavioral effect, which could be restored by GABA receptor antagonists into the ventral tegmental area (VTA). These findings suggest that the degree of cannabinoid receptor type 1 (CB1) receptor activation—and possibly the endogenous fluctuation in eCB transmission—can exert different effects on the mPFC-VTA loop, feedforward interneuronal processing within the VTA, and related behaviors (Figure 2A)
Neither input-output curves nor short-term forms of synaptic plasticity were affected by the WIN treatment. These findings indicate that the underpinnings of cannabinoid tolerance, i.e., CB1 receptor down-regulation or desensitization, can affect the prefrontal capacity to undergo long-term presynaptic plasticity without altering its basal intra-cortical transmission
Summary
Heavy cannabis use may precipitate or exacerbate schizophrenia symptoms. The substantial psychiatric documentation on this matter has been reviewed multiple times in the past two decades (Manseau and Goff, 2015). In another study (Bossong et al, 2013), THC has been linked with impaired performance in an executive task, which in turn has been correlated with reduced deactivation in brain regions related to the default mode network Overall, these studies suggest that phytocannabinoid-induced cognitive deficits, which resemble those of schizophrenia, involve brain-wide alterations (Bossong et al, 2013). Auditory processing studies have in turn shown reduced amplitude and phase locking of evoked beta (15–30 Hz) and gamma frequencies (Hirano et al, 2008; Johannesen et al, 2008; Roach and Mathalon, 2008) These results suggest an impaired ability to coordinate oscillatory activity and sensory responsivity, which may underlie the perceptual and cognitive deficits of schizophrenia (Uhlhaas and Singer, 2010). In vitro studies have provided all available information on eCB-mediated synaptic plasticity in the mPFC or hippocampus in schizophrenia-relevant assays (e.g., adolescent cannabinoid exposure, mGluR and CB2 knockouts, and acute psychostimulant effects)
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