Effects of intraperitoneal administration of the GABAB receptor positive allosteric modulator 2,6-di tert-butyl-4-(2-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) on food intake in non-deprived rats

Abstract

γ-Aminobutyric acid-B (GABAB) receptor positive allosteric modulators (PAMs) act on an allosteric site on the GABAB receptor to potentiate the effects of GABA and GABAB receptor agonists. It has previously been demonstrated that the GABAB receptor agonist baclofen increases food intake in non-deprived rats. The aim of this study was to investigate whether the GABAB receptor PAM 2,6-di tert-butyl-4-(2-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) would (i) increase food intake, and (ii) potentiate the hyperphagic effects of baclofen in rats. In Experiment 1, the effects of intraperitoneal (i.p.) administration of CGP7930 (1, 6 and 12mg/kg) was investigated on food intake in non-deprived male Wistar rats. The 12mg/kg dose of CGP7930 significantly increased cumulative food intake 30, 60 and 120min (P<0.05, in each case) after administration. The 1 and 6mg/kg doses were without effect. In Experiment 2, the effects of pretreatment with CGP7930 (6mg/kg; i.p.) 5min prior to administration of baclofen (2mg/kg, i.p.) was investigated on 30min cumulative food intake in non-deprived male Wistar rats. Baclofen (2mg/kg) significantly increased food intake compared with vehicle treatment (P<0.01). CGP7930 (6mg/kg) had no effect on feeding. However, pretreatment with CGP7930 (6mg/kg) significantly potentiated the hyperphagic effects of baclofen (2mg/kg) (P<0.01). These findings show that CGP7930 increases food intake and enhances the hyperphagic effects of baclofen, and are consistent with in vitro studies that suggest that it potentiates the effects of endogenous GABA and GABAB receptor agonists by allosteric modulation of the GABAB receptor.