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C Caccia

Publications and source records attributed to C Caccia.

23 records · Page 2Linked to original sources
PubMedDate not supplied

Dopamine receptors status after unilateral nigral 6-OHDA lesion. Autoradiographic and in situ hybridization study in the rat brain.

The physiological effects of dopamine (DA) are mediated by several distinct receptor subtypes. The effects of unilateral nigral 6-hydroxydopamine (6-OHDA) lesions on DA receptors were investigated by receptor autoradiography using the D1 selective ligand [3H]SCH 23390 as well as the D2 ligand [3H]spiroperidol. mRNA distribution was studied by in situ hybridization. Lesioned rats were sacrificed at different time intervals. Receptor binding studies were performed on tissue sections using selective ligands. [35S]UTP labeled RNA probes were prepared from the different cDNA (D1, D2, D3) and used for in situ hybridization. A specific loss of receptor binding sites and mRNA hybridization was found in the lesioned substantia nigra pars compacta (SNc) at all times examined. Receptor binding studies revealed a different time-dependent increase in both D1 and D2 receptors. In situ hybridization showed that only D2 receptor mRNA increased in the caudate-putamen (CPu) of the lesioned side 15 d after 6-OHDA. No changes were observed in D1 and D3 receptor mRNA during the entire time-course.

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PubMedDate not supplied

Effect of ergolines on neurotransmitter systems in the rat brain.

The interaction of nicergoline with various monoaminergic receptors and its effects on monoamine turnover were studied in specific rat brain areas in comparison with those of its metabolites, 10-methoxy-1,6-dimethyl-ergoline-8 beta-methanol (MMDL) and 10-methoxy-6-methyl-ergoline-8 beta-methanol (MDL). Nicergoline showed marked in vitro affinity for alpha 1-noradrenergic receptors (IC50 = 0.2 nM), less for alpha 2, S1 and S2 (IC50 about 10(-7) M). Its strong interaction with alpha 1-receptors was confirmed in vivo. The affinity of the other ergolines for alpha 1-receptors was lower than that of nicergoline. The level of monoamine metabolites (HVA and DOPAC for dopamine, MOPEG-SO4 for noradrenaline and 5-HIAA for serotonin) was taken as a measure of their turnover in the rat brain. A single dose of nicergoline (20 mg/kg, s.c.) strongly enhanced noradrenaline turnover, less that of dopamine. These effects, probably due to the interaction with alpha-receptors, were more marked after parenteral than oral administration. MMDL shared nicergoline's effect on dopamine and MDL that on noradrenaline, but they were less active than the parent compound. The most interesting results were obtained after chronic treatment (6-7 weeks) with rather low doses: 5 mg/kg b.i.d. of nicergoline and equimolar doses of the metabolites. Nicergoline and MMDL both enhanced dopamine turnover, especially in mesolimbic areas. In conclusion, the present report confirms and extends previous results on nicergoline's effects on catecholamine turnover and shows that its metabolite MMDL shares its effects on dopamine. Finally, it is particularly interesting that both ergolines were more effective in old than in young rats.

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