Effect of Valproic Acid on Food Intake and Nociception in Morphine-Dependent Mice

The anorectic and antinociceptive effects of valproic acid (VPA) were studied in morphine- dependent mice in comparison with normal ones. For this purpose, the food intake of animals deprived of food for 24 hours and the hot plate reaction time, were studied. Morphine-dependency was induced by i.p. injections of morphine HC1 (40 mg /kg; twice daily for 3 days). Morphine- dependent animals showed a significant decrease in food intake (p 0.05), when compared with control mice (non-morphinized). Acute administration of VPA (100, 200 and 300 mg /kg, i.p.) significantly potentiated the anorexia observed in morphine-dependent mice. VPA (200 and 300 mg /kg, i.p.) alone produced a significant decrease in food intake (p 0.05) in non-morphinized animals. In the study of antinociception, a significant increase (p 0.001) in hot-plate latency was observed in morphine-dependent animals, as compared to control mice. Treatment with VPA alone produced a significant increase (p 0.05) in hot-plate latency in saline-pretreated animals in comparison with saline-pre treated control group. However, the administration of VPA (100 and 200 mg /kg, i.p.) to morphine-dependent animals significantly decreased (p 0.05) their hot-plate latency as compared to the control group. In conclusion, VPA exhibited anorectic and antinociceptive activities in mice. VPA potentiated the anorexia seen in mice, which were rendered dependent to morphine, whereas the drug inhibited the antinociceptive activity observed in these mice. It seems from the present study that VPA is probably toxic in morphine-dependent subjects, since it might potentiate the anorectic and inhibit the analgesic effects.