Depletion of dopamine binding sites and changes in dopamine and dihydroxyphenylacetic acid levels in 17- and 90-day-old rat striatum after irreversible receptor antagonism.
Irreversible antagonism of dopamine (DA) receptors by the alkylating compound N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) results in a depression of DA agonist mediated behaviors in adult, but not preweanling rats. DA D1 and D2 receptors, dihydroxyphenylacetic acid (DOPAC) and DA levels were assessed in 17- and 90-day-old rats in order to identify a neurochemical mechanism for this difference. EEDQ caused a depletion in D1 and D2 receptors in both young and adult rats, with the depletion in adults being relatively greater. In both age groups, EEDQ caused an unexpected decrease in DA levels which returned to normal levels by 30 days post-injection. In addition, DOPAC levels of adult rats, but not rat pups, were elevated after EEDQ treatment. The depletion of endogenous DA levels must be considered when interpreting the effects of EEDQ. Age-dependent differences in DA metabolism may be important for understanding the ontogenetic differences in EEDQ's behavioral effects.
Crawford
C A
CA
Department of Psychology, University of Kentucky, Lexington 40506-0044.
McDougall
S A
SA
Rowlett
J K
JK
Bardo
M T
MT
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
D000317:Adrenergic alpha-Antagonists; D018492:Dopamine Antagonists; D011804:Quinolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; C000470:EEDQ; D004298:Dopamine