It has previously been shown that systemic administration of the benzodiazepine diazepam (which acts by enhancing the effects of endogenous GABA on GABA_A receptors), or the GABA_B receptor agonist baclofen, increases food consumption in non-deprived rats (see Ebenezer, 1990, Patel et al., 2003). However, there has been little attempt to investigate the effects of acute repeated injections of these drugs on food intake. The present study was undertaken to address this issue.

Experiment 1: Male Wistar rats (n=7; b. wt. 395 – 460g) were housed in groups of 3 and 4 and had free access to food and water at all times. During experimental trials, each rat received 3 successive i.p. injections of either physiological saline or baclofen (1 or 2 mg kg^-1) at 120 min intervals. The rats were placed singly in separate experimental cages immediately after the 1^st injection with free access to food and water for 360 min. Food intake was measured at 60 min after each injection, as described previously (Ebenezer, 1990). A repeated measures design was used with each rat receiving all treatments; 4 days separated successive drug trials. The data was analysed by ANOVA and Newman-Keuls post-hoc test.

Experiment 2: A similar experimental protocol as described for Experiment 1 was used except that the rats (male Wistar; n=8; b.wt. 380 – 450g) received either saline or diazepam (1 or 2 mg kg^-1).

Following the 1^st injection both doses of baclofen produced significant increases in food intake at 60 min (Expt. 1; Fig. 1). However, the 2^nd and 3^rd injection did not affect food intake when measured 60 min after these injections (Fig. 1). By contrast, both doses of diazepam significantly increased food intake 60 min after the 1^st, 2^nd and 3^rd injection (Expt. 2; Fig. 2). These results suggest that baclofen and diazepam act differently to increase feeding. Diazepam potentiates the effects of GABA on the ionotropic GABA_A receptor. Thus, it is likely that this GABA receptor subtype can be “switched on and off” fairly rapidly, and therefore repeated stimulation with diazepam can induce a new feeding response after each injection. On the other hand, the GABA_B receptor is a metabotropic receptor which activates G-proteins and intracellular signalling processes, and produces long term changes which may be reflected in the failure of baclofen to increase food intake with repeated injections separated by 2h.

 Fig. 1. Effects of repeated injections of baclofen.        Fig. 2. Effects of repeated injections of diazepam.

Ebenezer, I.S. (1990) NeuroReport, 1, 73 – 76.
Patel, S.M. et al. (2003) Br. J. Pharmacol. 140, 62P.