Effects of oxotremorine on convulsions in mice induced by scopolamine and food intake after fasting

Abstract

Antimuscarinic administration and food intake cause convulsions in mice and rats after fasting for 48 h or less. Increased M₁ and M₂ muscarinic receptor expression in brain regions during fasting, and reversal of changes by refeeding may contribute to these seizures. Since receptor expression is regulated in response to agonist stimulation, this study investigated effects of nonselective muscarinic receptor agonist oxotremorine on convulsions in fasted animals. Mice deprived of food for 24 h were given oxotremorine during (0.1 mg/kg, twice daily, s.c.) or after (0.05 or 0.1 mg/kg, i.p.) fasting. Fasted animals were treated with saline or scopolamine (i.p.) and observed for 30 min for the convulsions after being allowed to eat ad libitum. Oxotremorine administration during fasting produced no significant effect on convulsion development. Incidence and onset of convulsions, and seizure stages were indifferent between the scopolamine and oxotremorine - scopolamine groups. However, oxotremorine (0.1 mg/kg) administration after fasting reduced incidence of convulsions. Resulting from an agonist-antagonist interaction at M₁ and/or M₂ muscarinic receptors, oxotremorine administered after fasting exhibited an anticonvulsant activity. Oxotremorine administration during fasting was expected to suppress seizure development via inhibition of receptor expression. Results did not confirm this expectation and suggested that muscarinic receptor expression was either not affected or not related to the convulsions. Food intake after fasting, and food deprivation have been shown to induce cholinergic hyperexcitability. Although contrary to our hypothesis, future research may investigate whether increased expression of muscarinic receptors mediate or contribute to an increase in cholinergic activity.