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Therapeutic doses of amphetamine or methylphenidate differentially increase synaptic and extracellular dopamine
Author(s) -
Schiffer W.K.,
Volkow N.D.,
Fowler J.S.,
Alexoff D.L.,
Logan J.,
Dewey S.L.
Publication year - 2005
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20235
Subject(s) - microdialysis , raclopride , amphetamine , dopamine , methylphenidate , chemistry , extracellular , pharmacology , striatum , synaptic cleft , endocrinology , medicine , neurotransmitter , biochemistry , biology , receptor , psychology , attention deficit hyperactivity disorder , psychiatry
Methylphenidate (MP) and amphetamine (AMP) are first‐line treatments for attention‐deficit hyperactivity disorder. Although both drugs have similar therapeutic potencies, the stimulatory effect of AMP on extracellular dopamine (ECF DA) is greater than that of MP. We compared extracellular effects directly against synaptic changes. ECF DA was assessed by microdialysis in freely moving rodents and synaptic dopamine (DA) was measured using PET and [ 11 C]‐raclopride displacement in rodents and baboons. Microdialysis data demonstrated that MP (5.0 mg/kg, i.p.) increased ECF DA 360% ± 31% in striatum, which was significantly less than that by AMP (2.5 mg/kg, i.p.; 1398% ± 272%). This fourfold difference was not reflected by changes in synaptic DA. In fact, rodent PET studies showed no difference in striatal [ 11 C]‐raclopride binding induced by AMP (2.5 mg/kg, i.p.; 25% ± 4% reduction) compared with that by MP (5.0 mg/kg, i.p.; 21% ± 4% reduction). Primate PET experiments also showed no differences between AMP (0.5 mg/kg, i.v.; 24% ± 4% reduction) and MP (1.0 mg/kg, i.v.; 25% ± 7% reduction) induced changes in [ 11 C]‐raclopride binding potential. The similar potencies of MP and AMP to alter synaptic DA, despite their different potencies in raising ECF DA, could reflect their different molecular mechanisms. Synapse 59:243–251, 2006. Published 2005 Wiley‐Liss, Inc.