EFFECTS OF BACLOFEN ON WATER INTAKE INDUCED IN RATS BY SYSTEMIC ADMINISTRATION OF ISOPRENALINE.

Abigail Houston, John Wong, Ivor Ebenezer
University of Portsmouth, Portsmouth, United Kingdom

We have previously shown that systemic administration of the GABAB receptor agonist baclofen (bac) inhibits drinking in rats (Ebenezer et al., 1992). More recently, we have demonstrated that bac significantly attenuates the dipsogenic effects of centrally administered angiotensin ll (ang) and have speculated that the hypodypsic effect of bac may be due to suppression of a central angiotensin system (Houston et al., 2006). In the present study we investigated the effects of bac on isoprenaline-induced drinking. Isoprenaline (isopren) induces drinking by increasing circulating levels of ang (see Kucharczyk, 1986). Male Wistar rats (body weight: 300 – 320 g, n = 8) received each of the following treatments in a repeated measures design: saline (sal) followed by sal, sal followed by bac (2 mg kg-1), isopren (0.5 mg kg-1) followed by sal, and isopren (0.5 mg kg-1) followed by bac (2 mg kg-1). Both injections were given s.c; 15 min separated the two injections. Fifteen min after the 2nd injection, the rats were presented with water and intake measured at intervals over 120 min, as described previously (Ebenezer et al., 1992). The results were analysed by ANOVA and post-hoc Dunnett’s test and are illustrated in Fig. 1. Isopren pre-treatment significantly increased drinking at 15, 30, and 60 min (see Fig. 1). Bac significantly suppressed isopren induced drinking at 15, 30 and 60 min (Fig.1)

Fig. 1. Effects of baclofen on isoprenaline-induced drinking. Vert.lines rep. + s.e.m.

It has been proposed that isopren increases circulating ang by stimulating release of renin (an action at β1 receptors in the kidneys) .As ang produced in the periphery does not cross the blood brain barrier, isopren induced drinking is thought to be secondary to the activation of receptors in the circumventricular organs. The subfornical organ (SFO) is considered to be the major site at which blood borne ang induces drinking (Lind et al., 1982).The present results lend further support to the view that the hypodypsic effect of bac may be due to suppression of a central ang system (Houston et al., 2006).

Ebenezer, I.S. et al. (1992) Gen. Pharmacol., 23, 375 - 379

Houston, A. et al. (2006) Proc Br Pharmacol Soc at www.pA2online.org/abstracts/Vol4Issue2abst166P

Kucharczyk, J. (1986) Eur. J. Pharmacol., 124, 213 - 220

Lind, R.W. et al. (1982) Physiol.Behav., 52, 69 – 74