The effect of chronic administration of Fluoxetine on 8-Oh-DPTA-Induced Hypophagia in CFLP mice

Umar Burki, Ivor Ebenezer. University of Portsmouth, Portsmouth, United Kingdom.

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 is abolished following chronic treatment with the antidepressant drug fluoxetine, a selective serotonin reuptake inhibitor (SSRI; Tite et al., 2003, 2004). We suggested that chronic administration with fluoxetine desensitises central 5-HT 1A receptors that leads to the loss of effect of 8-OH-DPAT on food intake (Tite et al., 2003, 2004). The present study was undertaken to investigate the effect of chronic administration of fluoxetine on 8-OH-DPAT-induced hypophagia in the mouse in order to test whether similar results could be obtained in another species. Male CFLP mice (b.wt. 47 – 50g; n=16) were randomly divided into 2 equal groups. Mice in Group 1 (Control Group) were injected i.p. once daily with physiological saline solution for 28 days, while mice in Group 2 (Treatment Group) were injected i.p. once daily with fluoxetine (20 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 a palatable wet mash (Ebenezer et al ., 2003) and food intake measured for 15 min. On days 28 and 30 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 food consumption on days 28 and 30 were not significantly different and the baseline control values were expressed as the average of the measurement made on the two days. The results obtained are shown in Fig.1. ANOVA revealed that there was a significant interaction between the two groups of mice and their responses to saline and 8-OH-DPAT (F (1,14) = 5.8230, P<0.05), and indicate that chronic treatment with fluoxetine reverses the hypophagic effect of 8-OH-DPAT in CFLP mice fed a palatable wet mash. In a separate experiment we found that acute treatment with fluoxetine does not affect the suppressant effect of 8-OH-DPAT on feeding in mice (unpublished results) These findings extend previous observations in rat (Tite et al., 2004) to mouse and provide further behavioural support for the view that chronic exposure to SSRIs desensitise central 5-HT 1A receptors (Tite et al., 2003, 2004) in another rodent species.

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