Failure of amphetamine isomers to decrease hyperactivity in developing rats.
Possible amphetamine-induced changes in locomotor activity were investigated in developing rats administered intracisternal injections of 6-hydroxydopamine (6-OHDA) or its vehicle at 5 days of age. Administration of the dopamine neurotoxin resulted in a significant depletion of whole-brain dopamine to 44% of control levels, whereas norepinephrine levels were not significantly reduced. In normal and 6-OHDA-treated pups activity increased from moderately low levels at 15 days of age to moderately high levels at 25 days of age. However, 6-OHDA-treated rats were hyperactive at 20 days of age. At 25 days, activity in both groups was equal and declined to levels typical for adults. Administration of graded doses of d- and l-amphetamine generally increased activity in both groups of rats, with d-amphetamine being more potent than l-amphetamine. Furthermore, no dose of either amphetamine isomer decreased activity in 6-OHDA-treated, hyperactive rats. Hence, no convincing evidence was found for a "paradoxical calming" effect of amphetamine in hyperactive rats, supporting other recent reports. These results suggest that the neonatal DA-depleted rat does not provide an accurate model system for pre-clinical investigation of the human hyperkinetic syndrome.
D000375:Aging; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006892:Hydroxydopamines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D006892:Hydroxydopamines; D000661:Amphetamine; D003913:Dextroamphetamine; D004298:Dopamine; D009638:Norepinephrine