Interstitial 3‐Methoxytyramine Reflects Striatal Dopamine Release: An In Vivo Microdialysis Study

Previous ex vivo studies have provided indirect evidence that the dopamine (DA) metabolite 3‐methoxytyramine (3‐MT) may be a useful index of DA release in vivo. In the present study, in vivo microdialysis was utilized to assess directly the relationship between extracellular DA and 3‐MT in the striatum of rats following a variety of pharmacological manipulations. Apomorphine, a DA receptor agonist, produced a rapid, transient decrease in both DA and 3‐MT. Conversely, the DA receptor antagonist haloperidol produced a concomitant increase in extracellular DA and 3‐MT. Increases in DA and 3‐MT were also noted following the administration of the DA uptake inhibitor, bupropion. Local application of tetrodotoxin resulted in the complete elimination of measurable amounts of DA and 3‐MT in the dialysate. γ‐Butyrolactone also greatly decreased DA and 3‐ MT. Finally, d‐amphetamine produced a large increase in DA and 3‐MT in animals that had been treated previously with γ‐butyrolactone. The Pearson correlation coefficients for DA and 3‐MT following these manipulations ranged from 0.87 to 0.97. These data indicate that interstitial 3‐MT is an accurate index of DA release. However, when compared with previous ex vivo findings, the present results also suggest that changes in tissue concentrations of 3‐MT may not reliably reflect DA release following certain pharmacological manipulations.