Effects of the GABAB receptor agonist 3-aminopropyl (methyl) phosphinic acid on food intake in free feeding rats

Abstract

The GABAB agonist baclofen has been shown to increase food intake in rats by a GABAB receptor mediated mechanism. The present study, was undertaken to extend these observations by investigating the effects of intraperitoneal (ip) administration of the potent GABAB receptor agonist 3-aminopropyl (methyl)phosphinic acid (SKF97541) on food intake in free feeding rats. In the first experiment, male Wistar rats (n=6) received intraperitoneal (ip) injections of saline or SKF97541 (0.1, 0.2, or 0.4 mg / kg), with food intake monitored over 120 minutes. The results showed that the 0.1 and 0.2 mg/kg doses of SKF97541 significantly increased cumulative food intake at 120 min (at least P<0.05) whereas the 0.4 mg/kg dose had no acute effects on feeding. However, the 0.4 mg / kg dose produced ataxia and sedation in the rats and these effects may have competed with feeding behaviours. A second experiment was carried out to investigate this possibility. Rats (n=6 in each of two groups) received daily injections of either saline or SKF97541 (0.4 mg /kg, ip) for five days. By day 5, the rats developed tolerance to the sedative and ataxic effects, revealing a significant increase in food intake at 120 min compared to controls (P<0.05). The results obtained in this study with the potent GABAB agonist SKF97541 confirm and extend previous observations with baclofen and provide further support for a role of GABAB receptors in the regulation of food intake.