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Vol. 296, Issue 3, 876-883, March 2001
Department of Psychiatry, School of Medicine, University of
California at San Diego, La Jolla, California
The prescribed use of methylphenidate (Ritalin) in the treatment of
attention deficit hyperactivity disorder has risen dramatically in
recent years. The relative roles of dopamine, norepinephrine, and
serotonin in the therapeutic action of these drugs was assessed by
comparing the responses of extracellular nucleus accumbens dopamine and
serotonin and hippocampus norepinephrine to the acute administration of
low methylphenidate and amphetamine doses. The comparative
neurochemical profiles in response to methylphenidate and amphetamine
suggest that the norepinephrine effects may play an important role in
the therapeutic effects of low doses of psychostimulants. In addition,
to assess possible long-term consequences of prolonged exposure to this
drug, we examined whether changes in the locomotor response occurred
with repeated administration of these stimulant doses. Threshold doses
of methylphenidate (0.5-1.0 mg/kg) or amphetamine (0.1-0.25 mg/kg)
were administered twice daily, and then animals were tested in response
to 2.5 mg/kg methylphenidate or 0.5 mg/kg amphetamine. Our results
provide evidence that low-dose stimulant administration can result in
the development of behavioral sensitization, which is evident in
the subsequent behavioral response to the 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.
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