The Effect of Chronic Administration of Reboxetine on 8-OH-DPAT-Induced Hypophagia in Rats

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

We have previously reported that the inhibitory effect of the 5-HT1A receptor agonist 8-OH-DPAT on feeding in food-deprived rats or non-deprived rats given access to palatable food is attenuated following chronic treatment with selective serotonin reuptake inhibitors (SSRI; Tite et al., 2003) and monoamine oxidase inhibitors (MAOI; Burki et al., 2005). We suggested that chronic administration with these antidepressants desensitises central 5-HT1A receptors and results in the loss of effect of 8-OH-DPAT on food intake (Tite et al., 2003; Burki et al., 2005). The present study was undertaken to investigate the effect of chronic administration of the noradrenaline reuptake inhibitor antidepressant (NRI) reboxetine on 8-OH-DPAT-induced hypophagia in the rat. Male Wistar rats (b.wt. 310 – 390 g; n=12) were divided into 2 equal groups and were deprived of food in their home cages for 22 h each day. 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 reboxetine (4 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 food and water 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 for the rats chronically treated with saline (Group 1) was 2.2 ± 0.2g after saline and 1.3 ± 0.4 g (P<0.01) after 8-OH-DPAT. The mean ± s.e.mean food intake for the rats chronically treated with reboxetine (Group 2) was 2.1 ± 0.2g after saline and 1.8 ± 0.4 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) = 8.361, P<0.02), and indicate that chronic treatment with reboxetine reverses the hypophagic effect of 8-OH-DPAT in fasted rats. These findings extend previous observations and show that chronic administration of an NRI also reverses the inhibitory effects of 8-OH-DPAT in fasted rats. Although NRIs increase central levels of noradrenaline, there is some evidence that chronic administration of reboxetine may act indirectly to desensitise 5-HT1A receptors (see Harkin et al., 2005)). Thus, these data, taken together with previous studies (Tite et al., 2003, 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.

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Tite, R. et al. (2003) Br. J. Pharmacol., 140, 64P.