Acute and subchronic effects of gamma-hydroxybutyrate on isolation-induced aggression in male mice

Gamma-hydroxybutyrate (GHB) is a new drug with abuse potential popularly known as "liquid ecstasy". It is an endogenous compound of the mammalian brain which satisfies many of the criteria for consideration as a neurotransmitter or neuromodulator. Preliminary studies have found that GHB (100-200 mg/kg) reduces aggressive behavior in mice. This study was designed to assess the effects of low and intermediate doses of GHB (5, 25, 50 and 100 mg/kg, ip) on isolation-induced aggression in male mice, using an ethopharmacological approach. Moreover, the possible development of tolerance after its subchronic administration for 15 consecutive days was also examined. 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. Acute treatment with GHB (25-100 mg/kg) significantly reduced offensive behaviors (threat and attack) without affecting immobility, whereas with the lowest dose used (5 mg/kg) a significant increase of attack behaviors was observed. This behavioral profile was maintained when GHB (25-100 mg/kg) was administered during 15 consecutive days, indicating an absence of tolerance to the initial antiaggressive action of the drug. However, the subchronic treatment with 5 mg/kg of GHB produced an opposite effect to that observed after single treatment, suggesting a possible desensitization of postsynaptic dopaminergic receptors.