Effects of .DELTA.9-Tetrahydrocannabinol and Diazepam on Feeding Behavior in Mice.

Abstract

ABSTRACT. The present study examined effects of diazepam (DZP) alone or in combination with ∆9-tetrahydrocannabinol (THC) on feeding behavior as well as body weight in male ddY strain mice at 5 weeks of age. Because we saw no hyperphagic effect of DZP with or without THC in mice, we explored the hyperphagia elicitable by DZP. THC [2 (THC2) or 4 (THC4) mg/kg/day s.c.] was given daily for 7 days. For the last day the mice were starved and injected i.p. with DZP (2 mg/kg) 10 min prior to a food or maze test. Controls received vehicle injections. Feeding behavior was measured after giving food for 2 hr. THC4 significantly reduced body weight gain. DZP, with or without THC, induced hyperphagia. THC4 alone also induced hyperphagia that was not significantly affected by DZP. Time taken to find food was extended by DZP and further with THC. Both DZP and THC can therefore interact on food ingestion but synergize on food seeking in mice through different mechanisms.-KEY WORDS: diazepam, feeding behavior, hyperphagia, mouse, tetrahydrocannabinol.J. Vet. Med. Sci. 61(4): 351-355, 1999 (2 mg/kg: THC2, n=40, or 4 mg/kg: THC4, n=40) or 0.9% saline (n=40) for 7 days at 06:00 hr. On the 6th day of treatment, the mice were food-deprived from 09:00 to 09:00 on the 7th day. At 08:50 on the last day, DZP (2 mg/kg) or 0.9% saline solution was injected i.p. into half of the mice in both groups. Half of the mice administered DZP and half of the mice administered saline were given food at 09:00. Their food and water consumption were measured every 30 min for 2 hr. In the other half of each of the two groups the time to seek for food in a maze (time to banquet room) was measured. The statistical analysis was by analysis of variance (ANOVA). Differences were considered statistically significant at p values of less than 0.05. The data were then analyzed further by two-way Student's t-tests. RESULTSChronic DZP treatment, alone or in combination with THC, had no significant effect on body weight gain or daily food intake ( Figs. 1 and 2). DZP alone had no effect on the time to banquet room, but increased it in combination with THC (Fig. 3). THC4, but not THC2, reduced body weight gain (Fig. 4). The effect of THC2 on percentile gain of body weight was significant after 24-hr food deprivation (Fig. 5). Controls gained approximately 10% of their body weight during the 6 days prior to food deprivation. This gain was reduced by THC in a dose-dependent manner. After 24-hr food deprivation, the control group lost the 10% gained over the 6 days, but the THC group lost more weight in a dose-dependent manner.THC2, but not THC4, significantly reduced water ingestion (Fig. 6). The reduced water consumption caused by THC2 was significantly increased with simultaneous DZP. This facilitatory effect of DZP disappeared in combination with THC4. DZP had a significant hyperphagic effect on total food intake for 2 hr after 24 hr starvation, but * CORRESPONDENCE TO : NISHIMURA, M., Department of Pharmacology, University of Obihiro School of Veterinary Medicin...

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