Anti-aggressive effects of GHB in OF.1 strain mice: Involvement of dopamine D2 receptors

Numerous studies indicate that gamma-hydroxybutyric acid (GHB) influences the endogenous dopamine system. Both GHB and most dopaminergic D2 receptor antagonists are effective anti-aggressive agents in animal models. The present study aimed to investigate the effects of GHB on agonistic behaviour and to implicate D2 dopamine receptor on these behaviours. For this purpose, the effects of GHB (80, 120 and 160 mg/kg, IP) and tiapride (60 mg/kg) administered alone or in combination were examined on agonistic behaviour elicited by ‘isolation’ in male mice. Individually housed mice were exposed to anosmic “standard opponents” 30 min after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. The administration of 80 and 120 mg/kg of GHB reduced threat without impairing motor activity, but the administration of 160 mg/kg of GHB or the co-administration of GHB + tiapride (a selective D2 receptor antagonist) significantly reduced threat and attack but concomitantly increased immobility. The co-administration of GHB + tiapride had different effects to those observed by the administration of these drugs separately. It is concluded that the anti-aggressive effect of GHB appears to be mediated, at least in part, by D2 dopamine receptors. This anti-dopaminergic activity is an indirect effect, probably induced by the activation of GHB receptors of low affinity, and in this way, this compound would reduce levels of dopamine without blockading of D2 postsynaptic dopamine receptors.