In vivo measurement of extracellular dopamine and DOPAC in rat striatum after various dopamine-releasing drugs; implications for the origin of extracellular DOPAC.
In order to further examine the likely origin of the dopamine (DA) metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), certain drugs known to release DA from different intraneuronal pools were tested for their effects on extracellular striatal DA and DOPAC levels by means of brain microdialysis in the halothane-anaesthetized rat. Amphetamine (10(-6) and 10(-5) M), nomifensine (10(-5) M), potassium chloride (30 and 60 mM), methylphenidate (10(-5) and 10(-4) M) and tyramine (10(-5) M), when added to the perfusion medium and administered locally into the striatum via the dialysis membrane, increased the level of DA in striatal perfusates during the 20 min of application. In comparison, the level of DOPAC in the perfusates was decreased by both amphetamine (10(-5) M) and potassium chloride (60 mM), but was not significantly changed by nomifensine, methylphenidate or tyramine. The effect of amphetamine (10(-6) M) and nomifensine (10(-5) M) on DA and DOPAC levels was further studied by administering the drugs over a longer period of time (3 X 20 min). Although both of these treatments produced a similar increase of DA, only amphetamine reduced the levels of DOPAC. DA (10(-4) but not (10(-5) M) increased the levels of DOPAC but this effect was also seen in DA-denervated animals. These data indicate that when the DA nerve terminal is exposed to drugs which release newly synthesized DA, DOPAC declines possibly because intraneuronal monoamine oxidase is deprived of its main substrate. We suggest that these findings support the hypothesis that a major portion of the DA metabolite, DOPAC, is derived from an intraneuronal pool of newly synthesized DA.
Zetterström
T
T
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Sharp
T
T
Collin
A K
AK
Ungerstedt
U
U
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000032:analysis* / Q000187:drug effects; D004298:Dopamine / Q000032:analysis*; D004347:Drug Interactions; D005110:Extracellular Space / Q000032:analysis*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D010648:Phenylacetates / Q000032:analysis*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D010648:Phenylacetates; D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D008774:Methylphenidate; D011189:Potassium Chloride; D000661:Amphetamine; D004298:Dopamine