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The effects of chronic administration of sertraline on 8-OH-DPAT-induced hypophagia in rats Previous experiments carried out in this laboratory have shown that the suppressant effect of the 5-HT1A receptor agonist 8-OH-DPAT on feeding in food-deprived rats or non-deprived rats given palatable food (Ebenezer et al., 2003) is abolished following chronic treatment with the antidepressant drug fluoxetine, a selective serotonin reuptake inhibitors (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 whether chronic administration of sertraline, another SSRI, would affect the hypophagic effects of 8-OH-DPAT. Male Wistar rats (b.wt. 310 – 395g, 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 were injected with sertraline (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 a palatable mash (Ebenezer et al., 2003) and food intake measured for 30 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 rats and their responses to saline and 8-OH-DPAT (F(1,10) = 14.3395, P<0.01), and indicate that chronic treatment with sertraline reverses the hypophagic effect of 8-OH-DPAT. It is noteworthy that the baseline food consumption in the rats treated with sertraline (Group 1) was significantly (P<0.05) lower than that of the control animals (Group 2). It was also noted that the gain in body weight of the rats treated with sertraline over the 28 day treatment period was approximately 8.7 % less that of the control animals. Similar results with regard to food consumption and weight gain in rats have been obtained after chronic treatment with fluoxetine (Tite et al., 2003, 2004). The results show that chronic administration with the SSRI sertraline abolishes the suppressant effects of 8-OH-DPAT on food intake in rats fed a palatable wet mash. These findings provide further behavioural support for the view that chronic exposure to SSRIs desensitise central 5-HT 1A receptors (Tite et al., 2003, 2004).
Fig.1. The effects of 8-OH-DPAT on food intake in rats chronically treated with saline (Group 1) or sertraline (Group 2). Vertical lines rep. + s.e.mean. Ebenezer et al. (2003) Meth. Find. Expt. Clin. Pharmacol.,25, 727 – 731 |
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