Dyskinetic potential of dopamine agonists is associated with different striatonigral/striatopallidal zif-268 expression

• Published in: Experimental neurology 2010-08, Vol.224 (2), p.395-402
• Main Authors: Carta, Anna R., Frau, Lucia, Pinna, Annalisa, Morelli, Micaela
• Format: Article
• Language: English
• Subjects: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - adverse effects; Animals; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine agonist; Dopamine Agonists - adverse effects; Dyskinesia; Dyskinesia, Drug-Induced - etiology; Dyskinesia, Drug-Induced - metabolism; Early Growth Response Protein 1 - biosynthesis; Early Growth Response Protein 1 - genetics; Early-gene; Electrodiagnosis. Electric activity recording; Globus Pallidus - drug effects; Globus Pallidus - metabolism; Indoles - adverse effects; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Nervous system; Neurology; Neurons - drug effects; Neurons - metabolism; Oxidopamine; Parkinson Disease, Secondary - etiology; Parkinson Disease, Secondary - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1 - agonists; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D3 - metabolism; RNA, Messenger - biosynthesis; Ropinirole; SKF-38393; Striatonigral; Striatopallidal; Substantia Nigra - drug effects; Substantia Nigra - metabolism
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2010.04.016

In the dopamine-depleted striatum, an altered post-synaptic signalling of efferent neurons might underline the onset of variable dyskinetic responses to dopaminergic agonists. We have previously shown that a subchronic treatment with the D1 agonist SKF-38393 and the D2 agonist ropinirole induces a dyskinetic response of high and low intensities respectively, in 6-hydroxydopamine-lesioned rats. Here, zif-268 mRNA expression was evaluated in striatonigral and striatopallidal neurons to assess a neurochemical marker of these different dyskinetic responses upon drug administration. Acute and subchronic SKF-38393 (3mg/kg) increased zif-268 expression per neuron in the striatonigral pathway, albeit the number of neurons displaying high early-gene levels was reduced by the subchronic treatment. Zif-268 mRNA in striatopallidal neurons was not affected by SKF-38393 treatments. In contrast, ropinirole (5mg/kg) did not alter zif-268 mRNA in striatonigral neurons acutely, whereas ropinirole decreased zif-268 mRNA subchronically. Both acute and subchronic ropinirole decreased zif-268 levels in the striatopallidal pathway. The differential expression of zif-268 in striatonigral and striatopallidal neurons might provide a biochemical correlate of the dyskinetic outcome displayed by SKF-38393 and ropinirole treatments, suggesting that evaluation of neuronal responses upon drug administration provides a tool for the preclinical characterization of dyskinetic potential beyond behavioural tests.