Studies on the Effects of Reserpine in Mice as Influenced by its Diluent

Abstract

The effects of dextroamphetamine sulfate and benzphetamine hydrochloride on locomotor activity in mice pretreated with reserpine varied depending on the reserpine preparations used. Pretreatment with reserpine suspended in aqueous 0.25 percent methylcellulose (pH 5.8) had little effect on the response to dextroamphetamine sulfate but decreased the response to benzphetamine hydrochloride. Pretreatment with a reserpine solution (pH 3.5) significantly enhanced the locomotor response to both compounds at the higher doses tested. The difference in effect produced by the reserpine preparations could not be explained on the basis of differences in brain amine levels at the time locomotor activity was measured since both preparations had depleted brain amines to the same extent. Further studies revealed that variations in pH of the reserpine diluent had a marked effect on brain reserpine levels, on brain amine levels when measured 1 hr. after reserpine administration, and on the rate of onset and intensity of ptosis produced in the mouse. The effects of dextroamphetamine sulfate and benzphetamine hydrochloride on locomotor activity in mice pretreated with reserpine varied depending on the reserpine preparations used. Pretreatment with reserpine suspended in aqueous 0.25 percent methylcellulose (pH 5.8) had little effect on the response to dextroamphetamine sulfate but decreased the response to benzphetamine hydrochloride. Pretreatment with a reserpine solution (pH 3.5) significantly enhanced the locomotor response to both compounds at the higher doses tested. The difference in effect produced by the reserpine preparations could not be explained on the basis of differences in brain amine levels at the time locomotor activity was measured since both preparations had depleted brain amines to the same extent. Further studies revealed that variations in pH of the reserpine diluent had a marked effect on brain reserpine levels, on brain amine levels when measured 1 hr. after reserpine administration, and on the rate of onset and intensity of ptosis produced in the mouse.