The Impact of CB2 Receptor Ligands on the MK-801-Induced Hyperactivity in Mice

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.

Keywords: CB2 receptor ligands; Cannabis use; Endocannabinoid system; MK-801; Mice; Schizophrenia.

Fig. 1

Effects of an acute JWH 133 or vehicle administration on the locomotor activity of mice. JWH 133 (0.05, 0.1, 0.25, 0.5, 1.0, and 2.0 mg/kg; ip) or vehicle were injected immediately before the test; n = 8–12; the means ± SEM; *p < 0.05; **p < 0.01; ***p < 0.001 vs. vehicle-treated control group; Bonferroni’s test

Fig. 2

Effects of an acute AM 630 or vehicle administration on the locomotor activity of mice. AM 630 (0.1, 0.25, 0.5, 1.0, and 2.0 mg/kg; ip) or vehicle were injected immediately before the test; n = 8–12; the means ± SEM; *p < 0.05; **p < 0.01; ***p < 0.001 vs. vehicle-treated control group; Bonferroni’s test

Fig. 3

Effect of JWH 133 on MK-801-induced hyperactivity in mice. Non-effective dose of JWH 133 (2.0 mg/kg, ip) or vehicle were administered 15 min prior to vehicle or effective (0.3 mg/kg, ip) (a) and (0.6 mg/kg, ip) (b) dose of MK-801. After the last injection, the mice were then tested in actimeters; n = 8–12; the means ± SEM; *p < 0.05; **p < 0.01; ***p < 0.001 vs. vehicle/vehicle-treated group; ^p < 0.05 vs. vehicle/MK-801(0.6 mg/kg)-treated group Bonferroni’s test

Fig. 4

Effect of AM 630 on MK-801-induced hyperactivity in mice. Non-effective dose of AM 630 (2.0 mg/kg, ip) or vehicle were administered 15 min prior to vehicle or effective (0.3 mg/kg, ip) (a) and (0.6 mg/kg; ip) (b) dose of MK-801. After the last injection, the mice were then tested in actimeters; n = 8–12; the means ± SEM; **p < 0.01; ***p < 0.001 vs. vehicle/vehicle-treated group; &p < 0.05; &&&p < 0.001 vs. vehicle/MK-801(0.3 mg/kg)-treated group; ^p < 0.05; ^^p < 0.01; ^^^p < 0.001 vs. vehicle/MK-801(0.6 mg/kg)-treated group; Bonferroni’s test