Discriminative stimulus effect of phenylephrine.

Abstract

Rats were trained to discriminate phenylephrine in a two-lever, food-motivated operant task by increasing the i.p. administered training dose from 0.8 to 2 mg/kg. Stable discrimination to 2 mg/kg phenylephrine was established and testing of 0.5-2.5 mg/kg was shown to be dose-responsive and allowed for a calculated ED50 value of 0.87 mg/kg. Administration of methoxamine (0.5-6 mg/kg), another alpha 1-adrenoceptor agonist, produced a dose-responsive generalization, whereas only the lowest (0.04 mg/kg) and highest (0.12 mg/kg) doses of the alpha 2-adrenoceptor agonist clonidine produced generalization in the phenylephrine-trained rats. Likewise, yohimbine (2.5-4.5 mg/kg) generalized, whereas pretreatment with prazosin (0.1-0.4 mg/kg), the alpha 1-adrenoceptor antagonist, dose-responsively decreased phenylephrine discrimination. The results would indicate that phenylephrine is capable of controlling differential responding in a drug discrimination paradigm and would suggest that this effect is centrally mediated. The possibility that peripheral administration of phenylephrine (Neosynephrine) affects the brain in chronic users of nasal decongestants is discussed.