Cannabinoid–glutamate interactions and neural oscillations: implications for psychosis. (11th January 2018)

• Record Type: Journal Article
• Authors: Sherif, Mohamed A.; Cortes‐Briones, Jose A.; Ranganathan, Mohini; Skosnik, Patrick D.
• Other Names: Mazaheri Ali guestEditor.; Slagter Heleen guestEditor.; Thut Gregor guestEditor.; Foxe John J. guestEditor.
• Is Part Of: European journal of neuroscience. Volume 48:Number 8(2018)
• Page Start: 2890
• Page End: 2902
• Publication Date: 2018-01-11
• Subjects: cannabinoids -- glutamate -- ketamine -- neural oscillations -- THC; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13800
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Preclinical and clinical data suggest that the cannabinoid and glutamatergic systems are implicated in the pathophysiology of schizophrenia (SZ), the prototypical psychotic disorder. This has led to distinct "cannabis" and "ketamine" models of SZ, respectively. However, these two models need not be mutually exclusive. Indeed, in several brain regions implicated in the putative neural circuitry of SZ (e.g., hippocampus, frontal cortex, cerebellum), cannabinoid receptor type 1 (CB1Rs) and glutamate N‐methyl‐D‐aspartate receptors (NMDARs) have direct and indirect interactions. CB1R agonists and NMDAR antagonists act upon gamma‐aminobutyric acid (GABA) interneurons to reduce GABAergic neurotransmission. This would be predicted to result in the unsynchronized activity of pyramidal neurons, disrupting neural network oscillations involved in information processing, thus leading to psychotomimetic effects. Hence, the overarching aim of the current review is to synthesize the known literature on cannabinoids and glutamate in the context of neural oscillations in SZ. First, discussion of SZ and the basic mechanisms of neural oscillations are discussed, including a summary of the role of theta (4–7 Hz) and gamma (30–80 Hz) oscillations in neurocognition. Next, a brief review of the role of the cannabinoid and glutamatergic systems in SZ is outlined, followed by discussion of the known synaptic interactions between these two systems. Finally, the potential role of CB1Rs and NMDARs, both independently and in combination, on neural oscillations in relation to psychotic symptoms is considered. It is hoped that this review will yield a series of testable hypotheses that may be used to further elucidate the pathophysiology of SZ. Abstract : Data suggest that the cannabinoid and glutamatergic systems are implicated in the pathophysiology of schizophrenia (SZ). In several brain regions associated with SZ, cannabinoid receptor type 1 (CB1Rs) and glutamate N‐methyl‐D‐aspartate receptors (NMDARs) have direct and indirect interactions. CB1Rs and NMDARs act upon gamma‐aminobutyric acid (GABA) interneurons to reduce GABAergic neurotransmission, which could disrupt neural network oscillations and lead to psychotic symptoms.