It has previously been shown that both systemic and central administration of the GABA_B receptor agonist baclofen increases food consumption in non-deprived rats (Ebenezer, 1990; Ebenezer et al., 1992). More recently, experiments in this laboratory have indicated that endogenous central GABA acting at GABA_B receptors plays a physiological role in the regulation of food intake (Patel et al., 2003). Experiments were undertaken to extend these observations: (a) Systemic administration of baclofen increases food intake, and it is not inconceivable that stimulation of peripheral GABA_B receptors may contribute to the hyperphagic effect of the drug. The first part of this study was carried out to answer this question using the GABA_B agonist 3-aminopropylphosphinic acid (3-APA) which does not enter the brain from the systemic circulation (Hills et al., 1998) (b) Baclofen increases food intake in non-deprived rats, but there is a paucity of information on its effects on food-deprived rats. The second part of the study was conducted to investigate this issue.

Experiment 1. Male Wistar rats (n=8; b. wt. 300 - 320g) were housed in groups of 4 and had free access to food and water at all times. During experimental trials, the rats were injected i.p. with either saline or 3-aminopropylphosphinic acid (3-APA; 0.5, 1 or 2mg kg^-1) and placed singly in separate experimental cages with free access to food and water. Food intake was measured, as described previously (Ebenezer, 1990). A similar protocol was used in a separate group of rats (n=8; b. wt., 340 - 410g) except that they received baclofen (2 and 4 mg kg^-1) instead of 3-APA. Experiment 2. Male Wistar rats (n=8, b. wt. 300 - 390g) were housed in groups of 4 and were fasted for 22h each day. During experimental trials, the rats were injected i.p. with either saline or baclofen (1 or 2 mg kg^-1) and food intake measured. In all experiments, a repeated measures design was used with each rat receiving all treatments for the particular experiment; 3- 4 days separated successive trails. The data was analysed by ANOVA with repeated measures.

The results obtained in Experiment 1 with 3-APA show that none of the doses increased food intake. For example, mean food intake (g) ± s.e. mean at 60 min were as follows: Saline 1.8 ± 0.5; 0.5 mg kg^-1 3-APA 1.9 ± 0.7 (ns); 1 mg kg^-1 3-APA 1.3 ± 0.5 (ns) ;2 mg kg^-1 3-APA 1.4 ± 0.7 (ns). 3-APA did not produce any overt abnormal behaviours. By contrast, both doses of baclofen increased food intake in the non-deprived rats. Thus, mean food intake (g) ± s.e. mean at 60 min were as follows: Saline 2.2 ± 0.4; 1 mg kg^-1 baclofen 4.0 ± 0.2 (P<0.01); 2 mg kg-1 baclofen 3.6±0.4 (P<0.01). The results with the potent GABA_B agonist 3-APA, which cannot enter the brain from the systemic circulation, suggest that stimulation of peripheral GABA_B receptors do not cause an increase in food intake. Interestingly, baclofen did not affect feeding in fasted rats. Thus, for example, mean food intake (g) ± s.e. mean at 60 min were as follows: Saline 9.1 ± 1.2; 1 mg kg^-1 baclofen 12.0 ± 1.5 (ns) ; 2 mg kg^-1 baclofen 10.1 ± 1.2 (ns). These results indicate that the hungry animals were probably eating maximally and baclofen could not induce further increases in food intake. Further experiments using shorter periods of food deprivation may throw additional light on the manner by which GABA_B agonists affect feeding behaviour.

Ebenezer, I.S. (1990) NeuroReport, 1, 73 - 76.
Ebenezer et al. (1992) Neuropharmacol., 31, 39 - 42.
Hills, J.M. et al. (1989) Br. J. Pharmacol., 1292 - 1296.
Patel, S.M. et al. (2003) Br. J. Pharmacol., 140, 62P.