RESUMO
Although dopamine replacement therapy with L-DOPA in Parkinson's disease initially reduces motor symptoms, its chronic use often leads to the development of abnormal involuntary movements known as L-DOPA-induced dyskinesia. Increasingly, research has indicated that non-dopaminergic neurons gain function in the parkinsonian brain, taking up and converting L-DOPA to dopamine and releasing it as a "false neurotransmitter". Although less explored, promiscuity between monoamine transporters may also modulate these processes. Therefore, in order to examine the differential roles of monoamine transporters in L-DOPA's behavioral effects, three tricyclic antidepressants (TCA) with graded affinity for serotonin (SERT) vs. norepinephrine (NET) transporters were tested in hemi-parkinsonian rats: clomipramine (SERT>NET), amitriptyline (SERT=NET), and desipramine (SERTAssuntos
Antidepressivos Tricíclicos/uso terapêutico
, Discinesias/tratamento farmacológico
, Levodopa/uso terapêutico
, Transtornos Parkinsonianos/tratamento farmacológico
, Animais
, Corpo Estriado/metabolismo
, Dopamina/metabolismo
, Discinesias/fisiopatologia
, Levodopa/administração & dosagem
, Masculino
, Proteínas da Membrana Plasmática de Transporte de Norepinefrina/efeitos dos fármacos
, Oxidopamina/metabolismo
, Transtornos Parkinsonianos/fisiopatologia
, Ratos
, Ratos Sprague-Dawley
, Proteínas da Membrana Plasmática de Transporte de Serotonina/efeitos dos fármacos