Similar effects of amphetamine and methylphenidate on the performance of complex operant tasks in rats.
Methylphenidate and D-amphetamine are central nervous system stimulants that have been suggested to share certain behavioral and neurochemical effects. The current study was undertaken to determine whether methylphenidate and D-amphetamine have similar effects on the performance of a battery of complex operant tasks in rats. Thus, the effects of amphetamine (0.1-6.0 mg/kg, i.p.) and methylphenidate (1.12-18.0 mg/kg, i.p) on the performance of rats in three complex food-reinforced operant tasks were examined. The tasks (and the brain functions they are intended to model) included: (1) conditioned position responding (auditory/visual/position discrimination); (2) incremental repeated acquisition (learning); and (3) temporal response differentiation (time estimation). In addition, each of these tasks was paired with a progressive ratio task to assess drug effects on the rats' motivation to lever press for the food reinforcers used. Consistent with their effects in other behavioral paradigms, methylphenidate and D-amphetamine produced very similar patterns of disruption of the four tasks. Drug-induced changes in the endpoints of the progressive ratio task generally paralleled changes in the other three tasks, suggesting a major role for appetitive motivation in the effects of these agents. Several effects of these agents seen in the current study are consistent with their effects in children with attention-deficit-hyperactivity disorder. These data further validate the use of this battery of operant tasks for the characterization of pharmacological agents, and suggest that findings using these tasks may be predictive of what is seen in humans.
Mayorga
A J
AJ
Food and Drug Administration, National Center for Toxicological Research, Division of Neurotoxicology, HFT-132, Jefferson, AR 72079- 9502, USA. amayorga@nctr.fda.gov
Popke
E J
EJ
Fogle
C M
CM
Paule
M G
MG
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D008774:Methylphenidate / Q000494:pharmacology*; D009042:Motivation; D009949:Orientation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013998:Time Perception / Q000187:drug effects
D002395:Catecholamines; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D000661:Amphetamine