Does endogenous GABA acting on general GABAB receptors play a tonic role in the control of food intake? S.M. Patel & I.S. Ebenezer. Neuropharmacology Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, PO1 2DT, U.K.

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It has previously been reported that intracerebroventricular (icv) administration of the GABA_B receptor agonist baclofen increases food intake in rats and pigs by a central mechanism of action (Ebenezer, 1990; Ebenezer et al., 1990). However, it is not known whether endogenous GABA acting on central GABA_B receptors plays a physiological role in the regulation of food intake. The present study was undertaken to investigate this possibility.

Experiment 1. Male Wistar rats (b. wt. 300 - 340g, n = 5) were chronically implanted with icv cannula directed towards the lateral cerebral ventricle, as described previously (Ebenezer, 1990). During experimental sessions, the rats were food deprived for 22h and injected icv with either physiological saline or 5 µg of the GABA_B agonist CGP35348 (Olpe et al., 1990). Immediately after injection, the animals were placed singly in experimental cages with free access to food and water, and food intake measured for 120 min. The animals received both treatments in a cross-over design and 2 days separated successive trials.

Experiment 2. Male Wistar rats (b. wt. 300 - 330g, n = 16) were divided into two equal groups. The rats in Group 1 (Control Group) received daily i.p. injections of saline for 58 days. The rats in Group 2 (Treatment Group) were injected i.p. with baclofen (4 mg kg^-1) daily for 63 days. At the end of this period, the animals were food deprived for 22h and both groups of rats injected i.p. with physiological saline and placed in experimental cages with free access to food and water. Food intake was measured for 60 min.

The results from Experiment 1 are shown in Fig. 1. ICV administration of CGP35348 (5 µg) produced a significant decrease in food intake during the 30 min measurement period. The data from Experiment 2 show that the rats that were chronically treated with baclofen (Treament Group) ate significantly less food than the rats chronically treated with saline (mean cumulative food intake ± s.e. mean at 60 min: Control group 9.9 ± 0.6g, Treatment Group 8.3 ± 0.7 g, P<0.05).

Fig. 1. The effects of icv administration of GCP35348 (5 mg).on food intake in 22h fasted rats. Vertical lines rep. s.e. mean. *P<0.05, **P<0.01 (paired t-test).

The results obtained in Experiment 1 show that blocking central GABA_B receptors decreases food intake and suggest that endogenous GABA acting at central GABA_B receptors has a tonic role in the control of food intake. This view is further reinforced by the findings in Experiment 2. Evidence in the literature indicates that chronic administration of baclofen down regulates central GABA_B receptors (Malcangio et al., 1995). The observations that rats chronically, but not acutely (unpublished data), treated with baclofen display a reduction in food intake, suggest that this may be due to a down regulation of central GABA_B receptors which, may in turn, decrease the effects that endogenous GABA plays in regulating food intake.

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