The Roles of Dopamine Receptor and Adrenoreceptor on the Inhibition of Gastric Emptying and Intestinal Transit by Amphetamine in Male Rats

Abstract

Amphetamine, a central nervous stimulant, acts on the central nervous system (CNS) by increasing levels of norepinephrine, serotonin and dopamine (DA) in the brain. It stimulates the colonic motility and gastrointestinal (GI) function via the brain-gut connections as well as diminishes appetite to control bodyweight, but the mechanism between amphetamine and GI motility was unclear. We investigated the role of DA receptor and adrenoreceptor in the inhibitory effects of amphetamine on GI motility in male rats. After fasting overnight, the male rats received an intraperitoneal (i.p.) injection of amphetamine (3 mg/ml/kg) 15 min after i.p. injection of different antagonists for dopamine receptors and adrenoreceptors. Gastric emptying and intestinal transit were assessed 15 min after intragastric instillation of a test meal containing radioactive Na₂⁵¹CrO₄ and 10% charcoal. Haloperidol, a DA receptor antagonist, acting exactly as the selective D₂ receptor antagonist, eticlopride, completely prevented amphetamineinduced inhibition of gastric emptying and intestinal transit in male rats. The selective D₁ receptor antagonist, SCH 23390, significantly attenuated the amphetamine-induced inhibition of gastric emptying and intestinal transit in male rats. Both selective and nonselective α adrenoreceptor antagonist, phentolamine, prazosin and yohimbine, did not reverse the inhibitory effects of amphetamine on gastric emptying and intestinal transit. Propanolol, a β adrenoreceptor antagonist, partially attenuated the amphetamine-induced inhibition of gastric emptying but did not significantly attenuate intestinal transit. These results suggest that amphetamine-induced inhibition of gastric emptying and intestinal transit is mediated by an action on dopaminergic mechanism and adrenoreceptor with little involvement. These findings may clarify the influence of central nervous stimulant on GI tract and may provide the appropriate medication in CNS.