Abstract
It has been known that there is a relationship between cannabis use and schizophrenia-related symptoms; however, it can be a subject of controversy. The involvement of CB1 receptor ligands in the schizophrenia has already been revealed and confirmed. However, there is still lack of information concerning the role of CB2 receptors in the psychosis-like effects in mice and the further studies are needed.The aim of the present research was to study the role of the CB2 receptor ligands in the symptoms typical for schizophrenia. We provoked hyperlocomotion in mice which is analogous to positive psychosis-like effects in humans, by an acute administration of a NMDA receptor antagonist, MK-801 (0.3 and 0.6 mg/kg), a pharmacological model of schizophrenia. An acute administration of MK-801 induced the increase in locomotor activity (hyperactivity) in rodents, measured in actimeters.We revealed that an acute injection of CB2 receptor agonist JWH 133 at the dose range (0.05–1.0 mg/kg) and CB2 receptor antagonist, AM 630 at the dose range (0.1–1.0 mg/kg) decreased locomotion of mice. An acute injection of JWH 133 (2.0 mg/kg) and AM 630 (2.0 mg/kg) had no statistical significant influence on the locomotor activity of mice. However, an acute injection of both CB2 receptor ligands (agonist and antagonist), JWH 133, at the non-effective dose of 2.0 mg/kg and AM 630 at the non-effective dose of 2.0 mg/kg, potentiated the MK-801-induced hyperactivity.The present findings have confirmed that endocannabinoid system, not only via CB1, but also via CB2 receptors, may be involved in the schizophrenia-like responses, including hyperlocomotion in mice.
Highlights
Schizophrenia is a chronic mental disorder that combines a variety of clinical symptoms, including positive, negative, and cognitive symptoms (Lewis and Lieberman, 2000)
We revealed that an acute injection of CB2 receptor agonist JWH 133 at the dose range (0.05–1.0 mg/kg) and CB2 receptor antagonist, AM 630 at the dose range (0.1–1.0 mg/kg) decreased locomotion of mice
Mice were acutely injected with MK-801 inducing hyperlocomotion which correlates with the psychomotor agitation seen in schizophrenia patients (Bubenikova-Valesova et al 2010; Nestler and Hyman 2010)
Summary
Schizophrenia is a chronic mental disorder that combines a variety of clinical symptoms, including positive (e.g., hallucinations, psychosis), negative (e.g., amotivation, anhedonia), and cognitive (e.g., deficits in attention and memory) symptoms (Lewis and Lieberman, 2000). CB1 receptors are widely distributed in the central nervous system (CNS), especially in the limbic system and on the brain areas related to emotional responses, including basal ganglia, amygdala, cerebellum, hippocampus, and prefrontal cortex. Due to localization of CB (CB1 as well CB2) receptors, endocannabinoid system is able to modulate many cognitive- and emotional-related responses in the CNS, e.g., stress, anxiety, mood, and aggressive behavior. This system plays an important role in the pathology of many CNS-related disorders, such as depression, memory loss, and schizophrenia (Grotenhermen 2004)
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