The Effect of Chronic Oral Administration of Fluoxetine on 8-OH-DPAT-Induced Suppression of Food Intake in Rats

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

We have previously shown that chronic i.p. injections of the selective serotonin uptake inhibitor (SSRI) fluoxetine over a period of 28 days abolishes the hypophagic effect of the 5-HT1A receptor agonist 8-OH-DPAT in rats given access to palatable food (Tite et al., 2004). We suggested that this was due to the desensitisation of central 5-HT1A receptors. The present study sought to extend these findings by investigating whether chronic oral administration of fluoxetine also abolishes the 8-OH-DPAT-induced hypophagia in rats. Male Wistar rats (n=16; body weight: 210 -300g) were divided into two equal groups. Rats in Group 1 (Control) received a palatable meal (5g) at 15.00h daily for 28 days. Rats in Group 2 were presented with a similar meal to which fluoxetine (10 mg kg-1) was added. The rats in both groups consumed all of their food. 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 a palatable food and water and food intake measured (see Burki et al. 2005 ). 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 in the control group at 30 min (Group 1) was 19.8 ± 1.7g after saline and 10.2 ± 2.4 g (P<0.01) after 8-OH-DPAT. The mean ± s.e.mean food intake for the rats chronically treated with fluoxetine (Group 2) was 17.9 ± 1.6g after saline and 20.6 ± 2.3 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(1,14) = 14.03, P<0.01), and indicate that chronic oral treatment with fluoxetine reverses the hypophagic effect of 8-OH-DPAT in non-deprived rats given access to palatable food. There were no significant changes in body weights in the 2 groups of rats over the course of the treatment period. At the end of the experiment the weights of the control rats had increased by 41.3 ± 2.3% whereas the weights of the fluoxetine treated animals had increased by 38.0 ± 2.4% (ns). This contrasts with the weight loss observed when fluoxetine is given i.p. (Tite et al. 2004; Burki and Ebenezer, unpublished data). The results of this study show that chronic oral administration of fluoxetine is as effective as chronic i.p. administration (Tite et al., 2004) in reversing the hypophagic effects of 8-OH-DPAT. These finding suggest that oral administration of antidepressants to rats in palatable food may be used as an alternative to daily injections in studies that are undertaken to investigate the effects of chronic administration of these compounds on brain and behaviour.

Burki, U. et al. (2005) Proc. British Pharmacol. Soc.at http://www.pa2online.org/Vol3Issue3abst029P.pdf
Tite, R.M. et al. (2004) Proc. British Pharmacol. Soc. at http://www.pA2online.org/Vol2Issue1abst014P.pdf