The effect of chronic administration of nefazodone on 8-OH-DPAT-induced hyperphagia in fasted rats

We have previously reported that the suppressant 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 (see Ebenezer et al., 2003) is abolished following chronic treatment with antidepressants, such as fluoxetine and sertraline, that selectively inhibit the reuptake of 5-HT (Tite et al., 2003, Burki et al., 2005) and have suggested that this effect is due to desensitisation of central 5-HT1A receptors. The present study was undertaken to extend these observations and investigate the effect of chronic administration of the antidepressant drug nefazodone on 8-OH-DPAT-induced hypophagia in rats. Nefazodone is a serotonin antagonist and reuptake inhibitor (SARI). The principle antidepressant mechanism of SARIs is to potently inhibit 5-HT2A receptors combined with a less potent blockade of 5-HT and noradrenaline re-uptake (Davis et al., 1997). Male Wistar rats (b.wt. 215 – 310 g; n = 12) were randomly 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 27 days, while rats in Group 2 (Treatment Group) were injected i.p. once daily with nefazodone (60 mg kg-1). On day 28 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 (Ebenezer et al., 2003) and food intake measured at 30 min. On day 27 a similar experimental protocol as described for day 28 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 results were analysed by 2-way ANOVA and post-hoc Dunnett’s test. The mean ± s.e.mean food intake per 100g body weight for the rats chronically treated with saline (Group 1) was 2.5 ± 0.2 g after saline and 0.7 ± 0.3 g (P