CB2 receptor agonism reverses MK-801-induced disruptions of prepulse inhibition in mice.
BACKGROUND
Whilst cannabinoid CB2 receptors were thought to exist predominantly in immune cells in the periphery, the recent discovery of CB2 receptors in the brain has led to an increased interest in the role of these central CB2 receptors. Several studies have reported an association with CB2 receptors and schizophrenia. Sensorimotor gating deficits occur in schizophrenia patients and can be induced in animals using psychotomimetic drugs such as N-methyl-D-aspartate (NMDA) receptor antagonists.


OBJECTIVE
The aim of this study was to investigate the effect of CB2 ligands on sensorimotor gating, either alone, or on sensorimotor gating deficits induced by the NMDA receptor antagonist MK-801 in mice.


METHODS
The effects of CB2 receptor ligands on prepulse inhibition (PPI), an operational measure of sensorimotor gating, alone or when administrated in combination with MK-801, in Balb-C mice were evaluated.


RESULTS
The CB2 receptor agonist JWH015 had no significant effect on PPI alone but reversed disruptions in PPI induced by MK-801. This effect was blocked by co-administration of the CB2 receptor antagonist AM630, but not by co-administration of the CB1 receptor antagonist AM251, indicating a CB2-mediated effect. The mixed CB1/CB2 receptor agonist JWH203 was partially able to reverse MK-801-induced PPI disruptions. Neither the CB2 receptor antagonist AM630 nor the CB1 receptor antagonist AM251 had any significant effect alone or on MK-801-induced disruptions in PPI.


CONCLUSIONS
CB2 receptor agonism reversed MK-801 disruptions in sensorimotor gating deficits in mice, indicating that CB2 agonism may have a protective effect against aspects of drug-induced psychosis.
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
Ramy
R
Khella
Jennifer L
JL
Short
Daniel T
DT
Malone
D000161:Acoustic Stimulation; D000818:Animals; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D065808:Prepulse Inhibition / Q000187:drug effects*; D011605:Psychoses, Substance-Induced / Q000517:prevention & control / Q000523:psychology; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D013216:Reflex, Startle / Q000187:drug effects*; D055139:Sensory Gating / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D016291:Dizocilpine Maleate; C094023:iodopravadoline