Depletion of catecholamines in the brain of rats differentially affects stimulation of locomotor activity by caffeine, d-amphetamine, and methylphenidate

Abstract

The purpose of this study was to assess the role of catecholamines in brain, in the stimulation of locomotor activity, induced by caffeine, as compared to the psychomotor stimulants d-amphetamine and methylphenidate. Adult male rats were pretreated with either (1) 2.5 mg/kg (i.p.) reserpine, 24 hr prior to testing of locomotor activity, (2) 50 mg/kg (i.p.) alpha-methyl- para-tyrosine (AMPT) 6 hr and 2 hr prior to testing of locomotor activity, (3) 200 μg/rat (i.c.v.) 6-hydroxydopamine (6-OHDA), or 25 mg/kg (i.p.) desmethylimipramine (DMI) and 200 μg/rat 6-OHDA (i.c.v.), 6–8 weeks prior to testing. Each treatment group had a matched control group. Levels of catecholamines in the forebrain were determined in each of the treatment and corresponding control groups. All rats were tested with doses of caffeine, d-amphetamine and methylphenidate (excluding the 6-OHDA-treated animals), administered in random order intraperitoneally 35 min before locomotor activity was measured for 30 min. Pretreatment with either reserpine or AMPT attenuated the stimulation of locomotor activity induced by caffeine and d-amphetamine but not that induced by methylphenidate. The dose-response curve for amphetamine was shifted downward and to the right by reserpine but was flattened by AMPT. The dose-response curve for caffeine was displaced downward in a similar manner by both reserpine and AMPT. Treatment with 6-OHDA or DMI + 6-OHDA produced the expected changes in the content of catecholamines in brain, but failed to modify dose-response curves for caffeine or amphetamine. Reversible depletion of catecholamines in brain with reserpine and AMPT differentiated the locomotor stimulant actions of caffeine from those of d-amphetamine and methylphenidate and confirmed previously reported differences between amphetamine and methylphenidate.