The effects of intraperitoneal and intracerebroventricular administration of the GABA B receptor antagonist CGP 35348 on food intake in rats

Abstract

In order to test the hypothesis that endogenous gamma-aminobutyric acid (GABA), acting at central GABA B receptors, plays a physiological role in the control of feeding behaviour, it was reasoned that blocking these receptors with a centrally active GABA B receptor antagonist should reduce food intake in hungry rats. In the present study, experiments were carried out to test this possibility using the GABA B receptor antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid (CGP 35348), which is water-soluble and can penetrate the blood–brain barrier from the systemic circulation. CGP 35348 (50 and 100 mg/kg, i.p.) had no effect on food intake in 22-h fasted rats, but a higher dose (i.e. 500 mg/kg., i.p.) significantly reduced cumulative food consumption. These findings are consistent with previous observations that high systemic doses of CGP 35348 are needed to block central GABA B receptors. However, to eliminate the possibility that the 500 mg/kg dose of CGP 35348 decreased food intake by a peripheral, rather than a central mode of action, further experiments were undertaken where the drug was given directly into the brain by the intracerebroventricular (i.c.v.) route. I.c.v. administration of CGP 35348 (5 and 10 μg) significantly decreased cumulative food intake food intake in rats that had been fasted for 22 h. By contrast, i.c.v. administration of CGP 35348 (10 μg) had no effect on water intake in 16-h water-deprived rats. The results indicate that CGP 35348 reduces food consumption in hungry rats by blocking central GABA B receptors in a behaviourally specific manner. These findings suggest that endogenous GABA acting at central GABA B receptors plays a physiological role in the regulation of feeding behaviour.