The effects of chronic administartion of fluoxetine on 8-OH-DPAT-induced hypophagia in fasted rats   Richard M. Tite, Melanie Down, Sabrina Jhugroo & Ivor S. Ebenezer. Neuropharmacology Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, PO1 2DT, U.K.

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It has been previously demonstrated that 5HT1A receptor agonist, such as 8-OH-DPAT and ipsapirone, inhibit food intake in fasted rats by an action at central 5-HT_1A receptors (Ebenezer, 1992; Arkle et al., 2001). It is also been reported that chronic administration of serotonin reuptake inhibitors (SSRIs), such as fluoxetine, desensitise both pre- and postsynaptic 5HT_1A receptors (see Pejchal et al., 2002). The present study was undertaken to investigate whether chronic administration of fluoxetine would affect the hypophagic effects of 8-OH-DPAT in fasted rats.

Male Wistar rats (b.wt. 300 - 340g; n=16) 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 (Treatment Group) were injected i.p. once daily with fluoxetine (10 mg kg^-1). Following treatment, the animals in both groups were fasted for 22h and injected s.c. with either saline or 8-OH-DPAT (100 µg kg^-1). Immediately after injection, the animals were placed singly in experimental cages and food intake measured over a 2h period. Each rat received both treatments in a random fashion.

The results are illustrated in Fig.1. The rats treated chronically with fluoxetine lost approximately 15% of their body weight over the 28 day treatment period compared with the animals chronically treated with saline (data not shown). 8-OH-DPAT significantly inhibited cumulative food intake in the rats chronically treated with saline (Control Group) at each of the measurement intervals over the 2h period (Fig. 1A). By contrast, 8-OH-DPAT did not significantly affect feeding at any of the measurement intervals in the rats chronically treated with fluoxetine (Treatment Group; Fig. 1B).

Fig. 1. The effects of 8-OH-DPAT (100 µg kg^-1; s.c.) on cumulative food intake in rats that had been (A) chronically treated with saline (Control Group) or (B) fluoxetine (Treatment Group). Saline 8-OH-DPAT.Vertical line rep. s.e. mean. **P<0.01 (paired t-test).

The results show that chronic administration with the SSRI anti-depressant drug fluoxetine abolishes the suppressant effects of 8-OH-DPAT on food intake in food-deprived rats. Similar results have been obtained with the tricyclic antidepressant drug des-imipramine. These finding provide behavioural support for the notion that chronic administration with antidepressant drugs desensitise central 5-HT_1A receptors. Furthermore, it is possible that the method described here may prove to be useful as a novel in vivo test to assess psychoactive compounds for antidepressant activity.

Ebenezer, I.S. (1992) NeuroReport 3, 1019-1022.
Arkle, M. et al. (2000) Eur. J. Pharmacol., 408, 273-276.
Pejchal, T. et al. (2002) Br. J. Pharmacol., 135, 1115-1122.