Effect of chronic administration of the serotonin and noradrenaline reuptake inhibitor (SNRI) duloxetine on 8-OH-DPAT-induced hypophagia in rats

Umar A Burki, Ivor S Ebenezer. University of Portsmouth, Portsmouth, Hampshire, United Kingdom

It has previously been reported that the hypophagic effect of the 5-HT1A receptor agonist 8-OH-DPAT on feeding in non-deprived rats given access to palatable food (see Ebenezer et al., 2003) is abolished following chronic treatment with the antidepressant drug fluoxetine, a selective serotonin reuptake inhibitor (SSRI; Tite et al., 2004). We suggested that chronic administration with fluoxetine desensitises central 5-HT1A receptors that results in the loss of effect of 8-OH-DPAT on food intake (Tite et al., 2004). The present study was undertaken to extend these observations by investigating the effect of chronic administration of the SNRI duloxetine on 8-OH-DPAT-induced hypophagia in the rat. Male Wistar rats (b.wt. 280 – 330 g; n = 12) were randomly divided into 2 equal groups. Rats in Group 1 (Control Group) were injected i.p. once daily with physiological saline solution for 28 days, while rats in Group 2 (Treatment Group) were injected i.p. once daily with duloxetine (10 mg kg-1). On day 29 the animals in both groups were injected s.c. with 8-OH-DPAT (100 μg kg-1) and placed singly in experimental cages with free access to palatable food and water (Ebenezer et al., 2003) and food intake measured. On day 28 a similar experimental protocol as described for day 29 was used except that the animals in both groups were injected with saline instead of 8-OH-DPAT in order to establish a control feeding baseline. The mean ± s.e.mean food intake per 100g body weight for the rats chronically treated with saline (Group 1) was 4.7 ± 0.3 g after saline and 2.5 ± 0.3 g (P<0.01) after 8-OH-DPAT. The mean ± s.e.mean food intake per 100 g body weight for the rats chronically treated with duloxetine (Group 2) was 5.3 ± 0.3 g after saline and 4.8 ± 0.6 g (ns) after 8-OH-DPAT. ANOVA revealed that there was a significant interaction between the two groups of rats and their responses to saline and 8-OH-DPAT (F(1,10) = 6.092, P<0.03), and indicate that chronic treatment with duloxetine reverses the hypophagic effect of 8-OH-DPAT in fasted rats. These findings extend previous observations and show that chronic administration of an SNRI reverses the inhibitory effects of 8-OH-DPAT in non-deprived rats given access to palatable food presumable by desensitising central 5-HT1A receptors (see Tite et al., 2004). Thus, these data, taken together with data obtained previously (Tite et al., 2004, Burki et al, 2005), suggest that the method described here may be useful as a novel in vivo test to assess psychoactive compounds for potential antidepressant activity.

Burki, U. et al. (2005) Proc. Br. J. Pharmacol. http://www.pa2online.org/ Vol3Issue3abst029P.
Ebenezer, I.S. et al. (2003) Meth. Find. Expt. Clin. Pharmacol., 25, 727 – 731.
Tite, R. et al. (2004) Proc Br Pharmacol Soc at http://www.pa2online org //Vol2Issue1abst 014P