Effect of tricyclic antidepressants on L-DOPA-induced dyskinesia and motor improvement in hemi-parkinsonian rats

Pharmacology, Biochemistry, and Behavior
M M ContiC Bishop

Abstract

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 (SERT<NET). Rats received 6-hydroxydopamine lesions and were primed with L-DOPA (12mg/kg, s.c.) to develop stable dyskinesia (N=19 of 26). In a series of studies, rats were administered TCAs (0, 7.5, 15 or 30mg/kg, i.p.) followed by L-DOPA (6mg/kg, s.c.) and were measured for dyskinesia using the abnormal involuntary movements scale as well as motor performance and activity using th...Continue Reading

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Citations

Jul 9, 2016·Progress in Neurobiology·Philippe De DeurwaerdèreMark J Millan
Jul 28, 2016·Neuropharmacology·Melissa M ContiChristopher Bishop
Dec 27, 2016·Frontiers in Neuroscience·Haruo Nishijima, Masahiko Tomiyama
Apr 24, 2020·Frontiers in Pharmacology·Elena Paredes-RodriguezCristina Miguelez

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