Locomotor effects of acute and repeated threshold doses of amphetamine andmethylphenidate: Relative roles of dopamine and norepinephrine

The prescribed use of methylphenidate (Ritalin) in the treatment of attenti on deficit hyperactivity disorder has risen dramatically in recent years. T he relative roles of dopamine, norepinephrine, and serotonin in the therape utic action of these drugs was assessed by comparing the responses of extra cellular nucleus accumbens dopamine and serotonin and hippocampus norepinep hrine to the acute administration of low methylphenidate and amphetamine do ses. The comparative neurochemical profiles in response to methylphenidate and amphetamine suggest that the norepinephrine effects may play an importa nt role in the therapeutic effects of low doses of psychostimulants. In add ition, to assess possible long-term consequences of pro-longed exposure to this drug, we examined whether changes in the locomotor response occurred w ith repeated administration of these stimulant doses. Threshold doses of me thylphenidate (0.5-1.0 mg/kg) or amphetamine (0.1-0.25 mg/kg) were administ ered twice daily, and then animals were tested in response to 2.5 mg/kg met hylphenidate or 0.5 mg/kg amphetamine. Our results provide evidence that lo w-dose stimulant administration can result in the development of behavioral sensitization, which is evident in the subsequent behavioral response to t he drug. The relevance of these data to the therapeutic uses of these drugs is discussed within the context of the many variables that can affect the behavioral and neurochemical responses to stimulants.