Clorgyline-induced increases in presynaptic DA: changes in the behavioral and neurochemical effects of amphetamine using in vivo microdialysis.
Microdialysis was used in behaving rats to further characterize the behavioral and regional dopamine (DA) response to the monoamine oxidase (MAO) inhibitor clorgyline and determine how MAO inhibition affects amphetamine (AMPH)-induced changes in behavioral and extracellular DA dynamics. Although clorgyline (4.0 mg/kg) did not significantly alter behavior, it produced prolonged increases in caudate and accumbens extracellular DA and 3MT and corresponding decreases in homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). Clorgyline pretreatment altered the behavioral response to both low (0.25 mg/kg) and moderate (2.5 mg/kg) doses of AMPH, which was characterized by a shift to more intense forms of stereotype and corresponding decreases in locomotion. The caudate and accumbens DA response to AMPH (0.25 mg/kg) was also significantly augmented, consistent with an increase in AMPH-releasable cytoplasmic DA. Thus, the potentiated DA response in clorgyline-pretreated animals may be responsible for the changes in the stereotypy profile. Possible implications of these observations for the augmented behavioral response observed with repeated AMPH administration are discussed.
Segal
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DS
Department of Psychiatry, University of California, San Diego, La Jolla 92093-0603.
Kuczenski
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R
Okuda
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C
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D003010:Clorgyline / Q000494:pharmacology*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects
D015102:3,4-Dihydroxyphenylacetic Acid; D000661:Amphetamine; D003010:Clorgyline; D004298:Dopamine; D006719:Homovanillic Acid