Concomitant short- and long-duration response to levodopa in the 6-OHDA-lesioned rat: a behavioural and molecular study - PubMed (original) (raw)
Concomitant short- and long-duration response to levodopa in the 6-OHDA-lesioned rat: a behavioural and molecular study
C Marin et al. Eur J Neurosci. 2007 Jan.
Abstract
The long-duration response (LDR) is a sustained improvement in parkinsonism due to chronic levodopa therapy and lasts after discontinuation of treatment. We have investigated the molecular changes that underlie the LDR in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion. Animals were treated for 22 days with levodopa or saline. Forelimb akinesia was evaluated prior and following a test dose of levodopa. Rotational behaviour was weekly evaluated. Levodopa induced an improvement in the parkinsonian limb akinesia that lasted for 48 h after withdrawal. A shortening in the duration of rotational behaviour was observed. After 3 days of washout, levodopa treatment maintained elevated striatal preproenkephalin mRNA expression, also inducing an increase in preprodynorphin (PDyn) and dopamine D-3 receptor mRNAs, but without any modification of the adenosine A(2A) mRNA expression induced by 6-OHDA. Levodopa reversed the lesion-induced increase in the expression of cytochrome oxidase mRNA in the subthalamic nucleus and glutamate decarboxylase mRNA in the pars reticulata of the substantia nigra. After 7 days of levodopa washout, the molecular markers show a decline in the basal ganglia evolving towards the parkinsonian state, being statistically significant for the striatal PDyn mRNA. This study characterizes the concomitant presence of the short-duration response and LDR to levodopa in the 6-OHDA model of parkinsonism and shows that the molecular changes induced by levodopa in the basal ganglia are not permanent and that this reversal after levodopa washout may be responsible for the gradual motor deterioration that characterize the LDR.
Similar articles
- Effects of early vs. late initiation of levodopa treatment in hemiparkinsonian rats.
Marin C, Aguilar E, Mengod G, Cortés R, Obeso JA. Marin C, et al. Eur J Neurosci. 2009 Sep;30(5):823-32. doi: 10.1111/j.1460-9568.2009.06877.x. Epub 2009 Aug 27. Eur J Neurosci. 2009. PMID: 19712101 - A new ethyladenine antagonist of adenosine A(2A) receptors: behavioral and biochemical characterization as an antiparkinsonian drug.
Pinna A, Tronci E, Schintu N, Simola N, Volpini R, Pontis S, Cristalli G, Morelli M. Pinna A, et al. Neuropharmacology. 2010 Mar;58(3):613-23. doi: 10.1016/j.neuropharm.2009.11.012. Epub 2009 Dec 4. Neuropharmacology. 2010. PMID: 19951715 - Inhibitory effect of 8-(3-chlorostryryl) caffeine on levodopa-induced motor fluctuation is associated with intracellular signaling pathway in 6-OHDA-lesioned rats.
Song L, Kong M, Ma Y, Ba M, Liu Z. Song L, et al. Brain Res. 2009 Jun 18;1276:171-9. doi: 10.1016/j.brainres.2009.04.028. Epub 2009 Apr 21. Brain Res. 2009. PMID: 19393228 - Medical treatment of amblyopia: present state and perspectives.
Campos EC, Fresina M. Campos EC, et al. Strabismus. 2006 Jun;14(2):71-3. doi: 10.1080/09273970600701044. Strabismus. 2006. PMID: 16760111 Review.
Cited by
- Dopamine dysregulation in a mouse model of paroxysmal nonkinesigenic dyskinesia.
Lee HY, Nakayama J, Xu Y, Fan X, Karouani M, Shen Y, Pothos EN, Hess EJ, Fu YH, Edwards RH, Ptácek LJ. Lee HY, et al. J Clin Invest. 2012 Feb;122(2):507-18. doi: 10.1172/JCI58470. Epub 2012 Jan 3. J Clin Invest. 2012. PMID: 22214848 Free PMC article. - Characterization of the resting-state brain network topology in the 6-hydroxydopamine rat model of Parkinson's disease.
Westphal R, Simmons C, Mesquita MB, Wood TC, Williams SC, Vernon AC, Cash D. Westphal R, et al. PLoS One. 2017 Mar 1;12(3):e0172394. doi: 10.1371/journal.pone.0172394. eCollection 2017. PLoS One. 2017. PMID: 28249008 Free PMC article. - Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease.
Duty S, Jenner P. Duty S, et al. Br J Pharmacol. 2011 Oct;164(4):1357-91. doi: 10.1111/j.1476-5381.2011.01426.x. Br J Pharmacol. 2011. PMID: 21486284 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous