Monoamine oxidase inhibitor-induced blockade of locomotor sensitization to quinpirole: role of striatal dopamine uptake inhibition.
Previous studies have shown that the monoamine oxidase inhibitor (MAOI) clorgyline, blocks locomotor sensitization to the D(2)/D(3) dopamine agonist quinpirole and sensitizes self-directed mouthing behavior in rats by a mechanism independent of MAO inhibition. However, clorgyline is also an inhibitor of striatal dopamine uptake, and this mechanism could account for the effect of clorgyline on quinpirole sensitization. To investigate this possibility, the effects of clorgyline and pargyline were examined. Of these two MAOIs, only clorgyline inhibits dopamine uptake in the striatum. Rats received subcutaneous injections of clorgyline (1 mg/kg), pargyline (10 mg/kg) or vehicle 90 min prior to each injection of quinpirole (0.5 mg/kg, s.c., x8, twice weekly) or saline. Clorgyline and pargyline blocked the development of quinpirole-induced locomotor sensitization and sensitized self-directed mouthing behaviors in quinpirole rats. Thus, it is unlikely that clorgyline blocks locomotor sensitization to quinpirole via an inhibition of striatal dopamine uptake. Both MAOIs increased dopamine metabolism in the striatum, showed opposite effects in the prefrontal cortex, and eliminated the correlation between prefrontal dopamine and striatal DOPAC content found in quinpirole sensitized rats. We suggest that clorgyline and pargyline may affect the behavioral and neurochemical response to quinpirole via a previously reported MAOI-displaceable quinpirole binding site, a site which we hypothesize serves as a 'switch' to select what motor output becomes sensitized to repeated injections of quinpirole.
Culver
K E
KE
Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, L8N 3Z5, Ontario, Canada.
Rosenfeld
J M
JM
Szechtman
H
H
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003010:Clorgyline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D019257:Quinpirole / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D013239:Stereotyped Behavior / Q000187:drug effects
D018491:Dopamine Agonists; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D019257:Quinpirole; D010293:Pargyline; D003010:Clorgyline; D004298:Dopamine