Behavioral and biochemical correlates of the dyskinetic potential of dopaminergic agonists in the 6-OHDA lesioned rat

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Anna R CartaMorelli Micaela

Abstract

Prolonged treatment with L-DOPA induces highly disabling dyskinesia in Parkinson's disease (PD) patients. In contrast, dopaminergic agonists display variably dyskinetic outcome, depending on pharmacokinetic/pharmacodynamic profile. The present study was aimed at assessing behavioral and biochemical correlates of intense or mild dyskinesia displayed by the different dopamine (DA) receptors stimulation in a rat model of PD. The effect of subchronic stimulation of the D(1) receptor by SKF38393, and the D(2)/D(3) receptor by ropinirole was evaluated in unilaterally 6-hydroxyDA-lesioned rats. Sensitization of contralateral turning (SCT) behavior and abnormal involuntary movements (AIMs) were assessed as behavioral correlates of dyskinetic responses. Opioid peptides mRNA in the dorsolateral striatum (dlStr) and glutamic acid decarboxylase (GAD67) mRNA content in globus pallidus (GP), were evaluated as an index of neuroadaptive changes occurring in the direct and indirect basal ganglia pathways. Subchronic SKF38393 caused AIMs and SCT whereas ropinirole elicited SCT only, indicating that both drugs induced some dyskinetic response, albeit of different type. Peptides mRNA evaluation in dlStr, showed that SKF38393 subchronic treatment w...Continue Reading

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Citations

Jan 31, 2013·Experimental Neurology·Nicolas MorinThérèse Di Paolo
Apr 23, 2009·Neurotoxicity Research·M L GregórioC Da Cunha
Dec 10, 2013·Expert Opinion on Investigational Drugs·Fabio Blandini, Marie-Therese Armentero
Aug 18, 2010·Experimental Neurology·Gilberto Fisone
Oct 2, 2009·Peptides·Richard J Bodnar
May 24, 2014·The International Journal of Neuropsychopharmacology·Maria MavrikakiPer Svenningsson
Apr 30, 2014·Journal of Neurochemistry·Rolf HeumannMicaela Morelli

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