TY - JOUR
T1 - Dopamine receptor agonists mediate neuroprotection in malonate-induced striatal lesion in the rat
AU - Armentero, Marie Thérèse
AU - Fancellu, Roberto
AU - Nappi, Giuseppe
AU - Blandini, Fabio
PY - 2002
Y1 - 2002
N2 - Mitochondrial bioenergetic defects are involved in neurological disorders associated with neuronal damage in the striatum, such as Huntington's disease and cerebral ischemia. The striatal release of neurotransmitters, in particular dopamine, may contribute to the development of the neuronal damage. Recent studies have shown that dopamine agonists may exert neuroprotective effects via multiple mechanisms, including modulation of dopamine release from nigrostriatal dopaminergic terminals. In rats, intrastriatal injection of malonate, a reversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, induces a lesion similar to that observed following focal ischemia or in Huntington's disease. In this study, we used the malonate model to explore the neuroprotective potential of dopamine agonists. Sprague-Dawley rats were injected systemically with increasing concentrations of D1, D2, or mixed D1/D2 dopamine agonists prior to malonate intrastriatal insult. Administration of increasing doses of the D2-specific agonist quinpirole resulted in increased protection against malonate toxicity. Conversely, the D1-specific agonist SKF-38393, as well as the mixed D1/D2 agonist apomorphine, conferred higher neuroprotection at lower than at higher concentrations. Our data suggest that malonate-induced striatal toxicity can be attenuated by systemic administration of dopamine agonists, with D1 and D2 agonists showing different profiles of efficacy.
AB - Mitochondrial bioenergetic defects are involved in neurological disorders associated with neuronal damage in the striatum, such as Huntington's disease and cerebral ischemia. The striatal release of neurotransmitters, in particular dopamine, may contribute to the development of the neuronal damage. Recent studies have shown that dopamine agonists may exert neuroprotective effects via multiple mechanisms, including modulation of dopamine release from nigrostriatal dopaminergic terminals. In rats, intrastriatal injection of malonate, a reversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, induces a lesion similar to that observed following focal ischemia or in Huntington's disease. In this study, we used the malonate model to explore the neuroprotective potential of dopamine agonists. Sprague-Dawley rats were injected systemically with increasing concentrations of D1, D2, or mixed D1/D2 dopamine agonists prior to malonate intrastriatal insult. Administration of increasing doses of the D2-specific agonist quinpirole resulted in increased protection against malonate toxicity. Conversely, the D1-specific agonist SKF-38393, as well as the mixed D1/D2 agonist apomorphine, conferred higher neuroprotection at lower than at higher concentrations. Our data suggest that malonate-induced striatal toxicity can be attenuated by systemic administration of dopamine agonists, with D1 and D2 agonists showing different profiles of efficacy.
KW - Apomorphine
KW - Basal ganglia
KW - Cytochrome oxidase
KW - Quinpirole
KW - SKF-38393
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=0036935103&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036935103&partnerID=8YFLogxK
U2 - 10.1006/exnr.2002.8033
DO - 10.1006/exnr.2002.8033
M3 - Article
C2 - 12504889
AN - SCOPUS:0036935103
VL - 178
SP - 301
EP - 305
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 2
ER -