Does 8-OH-DPAT mediate its suppressant effects on food intake in rats by producing malaise?

Marion Arkle, Ivor S. Ebenezer

University of Portsmouth, Portsmouth, UK

We have previously demonstrated that s.c. administration of the 5HT1A agonist 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT; DPAT), in the dose range 25 – 100 μg kg-1, reduces food intake in hungry rats by a 5-HT1A receptor mediated mechanism (see Ebenezer et al., 2007). However, it is possible that the drug could suppress food intake by an aversive action, i.e. by causing illness or malaise in the animals. The present study was therefore undertaken to investigate the effects of DPAT in a conditioned taste aversion experiment (CTA) in rats (see Ebenezer et al., 1992) to examine whether the drug could elicit its hypophagic effects by producing malaise. Rats (n=24) were deprived of water for 16h a day and were divided into 4 equal groups, designated as either saline, lithium chloride (LiCl), DPAT (50 μg kg-1) or DPAT (100 μg kg-1) treatment groups. Each animal was given 3 daily training sessions where they were presented with tap water and sucrose solution (12%w/v). During the third training session the total intake of tap water and sucrose solution (SS) was measured after 30 min. The next day, the rats were given 15 min access to SS and were then injected i.p. with either saline, LiCl (100 mg kg-1) or DPAT (50 or 100 μg kg-1) according to their designated treatment groups and returned to their home cages. 24 h later they were presented with water and SS and their intake measured for 30 min. The data was analysed by the paired t-test. Fig. 1A shows that on the 3rd training session, the rats in all 3 groups displayed a preference for SS compared with water. During the retention trial (Day 5) the rats injected with saline or DPAT (50 or 100 μg kg-1) displayed a preference for SS compared with water similar to that observed on Day 3 (Fig. 1B). However, when consumption of SS was paired with injection of LiCl, a known aversive agent (see Ebenezer et al., 1992), the rats showed passive avoidance of SS (Fig. 1B). This is because they probably associated the aversive effects of LiCl with drinking SS. These data shows that DPAT does not produce taste aversion in a CTA experiment and suggests that the suppressant effects of DPAT on feeding (Ebenezer et al., 2007) is not caused by drug-induced malaise.

Fig. 1A. Water and SS intake on Day 3. Fig. 1B. Water and SS intake on Day 5

Ebenezer, I.S. et al. (2007) Meths. Find. Expt. Clin. Pharmacol.

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