Chronic administration of amphetamine alters the effect of the GABAB receptor agonist baclofen on food intake in rats Ivor S. Ebenezer, Rugina Ali & Anna Ballantine. Neuropharma-cology Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, PO1 2DT, U.K.

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It has been previously reported that both central and systemic administration of the GABA_B agonist baclofen increases food intake in non-deprived rats (Ebenezer, 1990, Ebenezer et al., 1992). Recent evidence has suggested an involvement of the mesolimbic dopamine system in the baclofen-induced hyperphagic response (see Ward et al., 2000). As chronic administration of amphetamine can alter (i) the firing pattern of neurones within the mesolimbic system and (ii) GABA_B receptor transmission in the ventral tegmental area (VTA) where mesolimbic dopamine neurones originate (see Wolf, 2002), the present study was undertaken to investigate the effects of chronic administration of amphetamine on baclofen-induced hyperphagia in rats.

Male Wistar rats (n=16; b. wt. 320 - 350g) were divided into two equal groups. Rats in the Control Group received 12 once daily i.p.injections of saline, while rats in the Test Group were treated with amphetamine (5 mg kg^-1, i.p.). Two days after the end of the chronic treatment period, experimental sessions commenced. Rats in the both groups were injected i.p.with either saline or baclofen (2 mg kg^-1). All rats received both treatments in random order. Immediately after injection the rats were placed in experimental cages with free access to food and water for 120 min, and food intake measured and analysed as described previously (Ebenezer, 1990).

Fig. 1. Effect of baclofen on food intake in rats in the (A) Control Group and (B) Test Group.
Saline Baclofen (2 mg kg^-1). Vertical line rep. + s.e.mean. *P<0.05, ** P<0.01 (paired t-test).

The results are shown in Fig. 1. Rats in the both groups displayed a gradual increase in food consumption under control conditions (saline) over the 120 min measurement period. In the Control Group, baclofen produced significant increases in cumulative food intake at the various measurement intervals throughout the 120 min, with the greatest increase occurring during the first 30 min (see Fig. 1A). By contrast, in the Test Group, the effects of baclofen on food consumption followed a different pattern (see Fig. 1B). Baclofen did not significantly increases cumulative food intake at 30, 60 or 90 min, although the mean cumulative intake was higher than that of controls. However, at 120 min there was a significant increase in food intake. The data from this study indicates that chronic treatment with amphetamine delays the hyperphagic effects of baclofen. Electrophysiological studies have shown that firing rates of VTA dopamine neurones is increased for several days after discontinuing repeated administration of amphetamine (Wolf, 2002). Moreover, GABA_B receptor transmission is enhanced after withdrawal from amphetamine (Wolf, 2002). The present results therefore lend support to the suggestion that the mesolimbic dopamine system may be involved in the hyperphagic effects of baclofen.

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