Neurophysiological Traces of L-Dopa Induced Dyskinesia in the Bed Nucleus Of The Stris Terminalis of 6-OHDA Lesioned Rats
Di Prospero, Cynthia
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The gold standard treatment for Parkinson’s disease (PD), L-3,4-dihydroxyphenylalanine (l-dopa), results in involuntary movements referred to as l-dopa-induced dyskinesia (LID). The mechanisms of LIDs are poorly known and there is no current strategy to efficiently prevent or control LIDs. Recent evidence has found that the expression of several immediate early genes positively correlates with LID severity in a basal forebrain structure, the bed nucleus of the stria terminalis (BNST). Furthermore, evidence shows that dopamine D1-like receptor (D1R)-dependent overexpression of IEGs in the oval (ov) and juxtacapsular (jx) subregions of the BNST may contribute to this phenomenon. Therefore this study aimed to examine how a D1R agonist modulates synaptic transmission in the ov and jxBNST of rats with and without LIDs using in vitro electrophysiology. Male Sprague Dawley rats (n=34) surgically received unilateral 6-OHDA lesions (2.5 µl at 3µg/µl) in the medial forebrain bundle. Three weeks after lesioning and upon occurrence of PD symptoms as measured by a stepping test, rats received daily injections of saline, or l-dopa (6mg/kg, i.p.) in benserazide (15mg/kg, i.p.), or benserazide alone. Benserazide is a peripheral inhibitor of DOPA-decarboxylase used to increase the central availability of dopamine (DA) and is generally administered with l-dopa, and thus was used as our vehicle control. On the 10th injection day, rats were assessed for the severity of three subtypes of dyskinesia: forelimb (jerks of the contralateral forelimb), orolingual (twitches of the jaw and tongue) and axial (contralateral twisted posturing). Rats were then euthanized one hour post injection and whole cell patch clamping was done in both the jx and ov areas of the BNST. Chronic l-dopa treatment did not alter strength at excitatory synapses in the ovBNST or jxBNST as measured by AMPA/NMDA ratios. Likewise, L-dopa treatment had no significant effect also D1-mediated modulation of GABAA or AMPA synaptic transmission in either the ov or jx BNST. Together, the data suggest that neither change in strength at excitatory synapses or D1R-modulation of synaptic transmission in the ov or jxBNST are LID neurophysiological traces in this area of the rat brain.