Depletion of catecholamines in the brain of rats differentially affects stimulation of locomotor activity by caffeine, D-amphetamine, and methylphenidate.
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 micrograms/rat (i.c.v.) 6-hydroxydopamine (6-OHDA), or 25 mg/kg (i.p.) desmethylimipramine (DMI) and 200 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Finn
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IB
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322.
Iuvone
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PM
Holtzman
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SG
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004027:Diencephalon / Q000187:drug effects; D004298:Dopamine / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006892:Hydroxydopamines / Q000378:metabolism / Q000633:toxicity; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D008781:Methyltyrosines / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000032:analysis; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000378:metabolism; D013687:Telencephalon / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D002395:Catecholamines; D006892:Hydroxydopamines; D008781:Methyltyrosines; D008774:Methylphenidate; D002110:Caffeine; D019805:alpha-Methyltyrosine; D012110:Reserpine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D003913:Dextroamphetamine; D004298:Dopamine; D009638:Norepinephrine