Effects of Chronic Administration of the GABA-B Receptor Agonist Baclofen on 24h Food Intake and Body Weight in Rats

Ivor S Ebenezer. University of Portsmouth, Portsmouth, Hants, United Kingdom.

We have previously demonstrated that chronic i.p. administration of baclofen in the dose range 1 – 4 mg kg-1 increases short-term food intake in non-deprived rats without the occurrence of tolerance to the drug-induced hyperphagia (Ebenezer et al., 2008; Patel et al., 2008). However, unlike the 1 and 2 mg kg-1 doses used in these studies, the 4 mg kg-1 dose significantly reduces body weight gain. The present study was carried out to investigate the effects of chronic i.p. administration of baclofen (4 mg kg-1) on 24 h food intake and body weight in rats to determine whether the reduction in weight gain was due to effects on long term food intake. Adult male Wister rats (n = 16; starting body weights: 240 – 270 g) were divided into 2 equal groups and injected i.p. with either saline (Group 1) or baclofen (4 mg kg-1; Group 2) on a daily basis for 24 days. Following the 1st, 8th, 15th and 22nd injection of saline or baclofen, the rats were placed separately into experimental cages with free access to food and water and cumulative food intake measured 24h later. Body weight for each rat was also recorded and expressed as a percentage change relative to body weight on treatment Day 1. Analysis of the feeding data (ANOVA and post-hoc t-test) revealed that there was no significant differences in 24h food consumption between the control and baclofen treated group throughout the experiment. For example, after the 1st and 22nd injections, the 24h food intake (g) ± s.e. mean was as follows: 1st injection: 28.0 ± 1.2g for Group 1 (saline) and 26.8 ± 3.5g for Group 2 (baclofen; n.s.); 22nd injection: 27.9 ± 1.1g for Group 1 and 25.2 ± 1.4 g for Group 2 (n.s.). These results confirm and extend previous findings with a 2 mg kg-1 dose of baclofen on 24 h food intake (Ebenezer et al., 2008). In agreement with previous observations (Patel et al., 2008), the rats treated with the 4 mg kg-1 dose of baclofen showed significant decreases in weight gain relative to controls for the duration of the experiment. Thus for example, the % change in body weights ± s.e. mean on treatment Day 2, 10 and 20 were as follows: Treatment Day 2 – saline -0.7 ± -2.1, baclofen -2.1 ± 0.3 (P<0.01); Treatment Day 10 – saline 8.3 ± 0.9, baclofen 3.7 ± 1.5 (P<0.01); Treatment Day 20 - saline 16.2 ± 0.9, baclofen 11.0 ± 1.2 (P<0.01). These observations suggest that while baclofen (4 mg kg-1) increases short-term food intake in rats (Patel et al., 2008), it has no effect on long term (24 h) food consumption. Thus, the inhibitory effect of baclofen (4 mg kg-1) on body weight gain is not related to long-term suppression of food intake by the GABA-B receptor agonist. It is therefore likely that the effects of baclofen (4 mg kg-1) on food intake and body weight may be mediated by separate mechanisms.

Ebenezer, I.S. et al. (2008) Proc.Br.Pharmacol.Soc.@htpp:/www.pA2online.org/abstract/Vol6Issue-4abst135P.
Patel, S.M. et al. (2008) Eur. J. Pharmacol. 593, 68 – 72.