title: Effects and mechanism of action of isatin, a MAO inhibitor, on in vivo striatal dopamine release.
abstract: Isatin is an endogenous indole that inhibits monoamine oxidase (MAO), being more selective for MAO-B than MAO-A isoform. By inhibiting MAO, isatin increases dopamine levels in the brain and, in animal models of Parkinson's disease (PD) isatin is able to prevent dopamine depletion. Contradictorily, some studies indicate that isatin did not increase striatal dopamine levels, although it was able to improve the motor signs in PD model. Given these conflicting data, our aim was to study the effects and neurochemical mechanisms of action of isatin on in vivo dopamine release from rat dorsal striatum using brain microdialysis technique in conscious and freely moving animals. Our results showed that intrastriatal administration of 1, 5 or 10 mM isatin, for 1 h, significantly increased dopamine levels to 355 ± 104%, 700 ± 72%, and 1241 ± 146%, when compared with basal values, respectively. The highest concentration of isatin (10 mM) was used to investigate whether the dopamine overflow is due to an exocytotic release or due to a possible action on dopamine transporter (DAT). The removal of Ca(++) from medium, administration of TTX (10 μM), or pretreatment with reserpine (10 mg/kg) significantly decreased by 90%, 83%, and 78%, respectively, the effect of isatin on dopamine levels. The blockade of DAT with nomifensine (50 μM) did not alter the effect of isatin; and isatin significantly increased the depolarization-evoked release of dopamine. These results suggest that isatin-induced dopamine release depends on vesicular dopamine content, and takes place due to a previous entry of Ca(++) and terminal depolarization.
authors.affiliation: Department of Functional Biology and Health Sciences, Faculty of Biology, Campus Lagoas-Marcosende, University of Vigo, Vigo, Pontevedra, Postal Code 36310, Spain.
authors.forename: Lorenzo Antonio
authors.initials: LA
authors.lastname: Justo
authors.affiliation: Department of Functional Biology and Health Sciences, Faculty of Biology, Campus Lagoas-Marcosende, University of Vigo, Vigo, Pontevedra, Postal Code 36310, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Durán
authors.affiliation: Department of Functional Biology and Health Sciences, Faculty of Biology, Campus Lagoas-Marcosende, University of Vigo, Vigo, Pontevedra, Postal Code 36310, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alfonso
authors.affiliation: Department of Functional Biology and Health Sciences, Faculty of Biology, Campus Lagoas-Marcosende, University of Vigo, Vigo, Pontevedra, Postal Code 36310, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fajardo
authors.affiliation: Department of Functional Biology and Health Sciences, Faculty of Biology, Campus Lagoas-Marcosende, University of Vigo, Vigo, Pontevedra, Postal Code 36310, Spain. Electronic address: lilianfaro@uvigo.es.
authors.forename: Lilian Rosana F
authors.initials: LRF
authors.lastname: Faro
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007510:Isatin / Q000494:pharmacology*; D017551:Microdialysis / Q000379:methods; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D007510:Isatin; D004298:Dopamine
keywords: Brain microdialysis; Dopaminergic neurotransmission; Isatin; MAO inhibitor; Rat striatum