Effects of subcutaneous administration of the 5-HT1A receptor agonist 8-OH-DPAT on food intake in CFLP mice

Ivor S. Ebenezer & Ashya Surujbally. Neuropharmacology Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, PO1 2DT, U.K.

Previous studies have shown that systemic administration of the 5HT1A receptor agonist 8-hydroxy-2(di-n-proylamino)tetralin (8-OH-DPAT) produces hyperphagia in non food-deprived rat and pig (Dourish et al., 1985; Ebenezer et al., 2001). However, there is a paucity of information on the effects of 5-HT1A receptor agonists in mice. Preliminary studies carried out in our laboratory have indicated that 8-OH-DPAT increases food intake in C57BL6 mice (Ebenezer et al., 2006). The present study was undertaken to extend these findings and investigate the effects of subcutaneous administration of 8-OH-DPAT on food intake in another strain of mouse.

Expt 1 : Male CFLP mice (n = 16; b. wt. 35 – 50 g) were divided into two equal groups. The mice in the Control Group were injected s.c. with physiological saline, and those in the Treatment Group were injected s.c. with 8-OH-DPAT (50 - 200 μg kg-1). Food was presented 5 min after injection. The amount of food consumed was measured in mg at 30 min intervals over the120 min experimental period. The mice in the Treatment Group received all doses of 8-OH-DPAT in a repeated measures design while those in the Control Group received saline injections during each trial. Seven days separated successive trials. Expt 2: Male C57BL6 mice (n=16; b. wt. 42 – 52 g) were divided into two equal groups. During the experimental trials, the mice in Group 1 were injected s.c. with saline or the 5-HT1A receptor antagonist WAY 100635 (300 μg kg-1). The mice in the Group 2 were injected s.c. with 8-OH-DPAT (200 μg kg-1) or a solution containing WAY 100635 (300 μg kg-1) + OH-DPAT (200 μg kg-1). Food was presented 5 min after the injection. The amount of food consumed was measured 30 min after presentation. The mice in each group received both treatments designated to that group in a cross-over design. A period of 3 days separated successive trials. The results from both experiments were analysed by two-way ANOVA with repeated measures.The results from Expt. 1 showed that the 100, 200 & 400 μg kg-1 doses of 8-OH-DPAT produced significant increases in cumulative food intake at all measurement intervals. Thus, for example, cumulative food intake (mg) ± s.e.mean at 30 min: Saline 12.5 ± 8.3, 8-OH-DPAT (100 μg kg-1) 267.5 ± 61.4 (P<0.01); Saline 47.5 ± 26.3, 8-OH-DPAT (200 μg kg-1) 233.8 ± 53.1 (P<0.01) Saline 63.8 ± 31.7, 8-OH-DPAT (400 μg kg-1) 215.0 ± 58.2 (P<0.01); . The 50 μg kg-1 dose was without effect. The results for Expt. 2 showed that the 5HT1A antagonist WAY 100635 (Fletcher et al., 1996), had no effect on food intake when administered on its own. However, food intake (mg) ± s.e.mean increased from 42.5 ± 9.6 for saline to 325.0 ± 22.9 for 8-OH-DPAT (200 μg kg-1; P<0.01), and this hyperphagic reponse was abolished by WAY 100635 (food intake (mg) ± s.e.mean for WAY 100635 + 8-OH-DPAT = 98.7 ± 20.0). The results of this study show that systemic administration of 8-OH-DPAT produces a dose-related increase in food intake in non-deprived CFLP mice by an action at 5-HT1A receptors. These data extend previous observations with 8-OH-DPAT in C57BL6 mice (Ebenezer et al., 2006) and add further support for the view that 5-HT1A receptor agonists increase food intake in the mouse similar to that in rats (Dourish et al., 1985) and pigs (Ebenezer et al., 2001).

Dourish, C.T. et al. (1985) Brain Res. Bull. 15, 377 – 384.
Ebenezer, I.S. et al. (2006) Acta Pharmacol. Sinica, Suppl. 1, pp 90.
Ebenezer, I.S. et al. (2001) Physiol. Behav. 73, 223 – 227.
Fletcher, A. et al. (1996) Behav Brain Res., 73, 337 – 353.