Changes in the mRNA Levels of α2A and α2C Adrenergic Receptors in Rat Models of Parkinson's Disease and l-DOPA-Induced Dyskinesia

被引:12
作者
Alachkar, Amal [1 ]
Brotchie, Jonathan M. [2 ]
Jones, Owen T. [3 ]
机构
[1] Univ Aleppo, Fac Pharm, Dept Pharmacol, Aleppo, Syria
[2] Univ Hlth Network, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada
[3] Univ Manchester, Sch Biol Sci, Div Neurosci, Manchester M13 9PT, Lancs, England
关键词
Parkinson's disease; L-DOPA-induced dyskinesia; Alpha2A adrenoceptors; Alpha2C adrenoceptors; 6-OHDA; Gene expression; LEVODOPA-INDUCED DYSKINESIA; AGONIST-INDUCED DYSKINESIA; VENTRAL TEGMENTAL AREA; LESIONED PRIMATE MODEL; LOCUS-COERULEUS; ALPHA-2-ADRENERGIC RECEPTOR; ANTAGONIST IDAZOXAN; CEREBRAL-CORTEX; ALPHA(2)-ADRENOCEPTOR ANTAGONIST; NORADRENERGIC NEURONS;
D O I
10.1007/s12031-011-9539-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The changes in the mRNA levels of alpha(2A) and alpha(2C) adrenoceptors were investigated in unilateral 6-OHDA-lesioned rat model of Parkinson's disease and l-DOPA-induced dyskinesia using in situ hybridization. In the untreated 6-OHDA-lesioned rats, alpha(2A) expression was elevated in the locus coeruleus (160 +/- 8% and 142 +/- 8% in lesioned and unlesioned sides compared to the comparable side in sham-operated rats). Following long-term (21 days, twice daily) treatment with l-DOPA (25 mg/kg l-DOPA methyl ester plus benserazide 6.25 mg/kg) in 6-OHDA-lesioned rats, levels of alpha(2A) adrenoceptor mRNA in the locus coeruleus were decreased, compared to the 6-OHDA-lesioned rats, returning to the levels of alpha(2A) mRNA in the sham-operated rats. alpha(2A) adrenoceptor expression was not changed in other brain regions in any treatment group. There was no change in alpha(2C) expression in the rostral or caudal striatum in which the highest density of alpha(2C) mRNA is present. In conclusion, the data presented in this study demonstrate an increase in alpha(2A) adrenoceptor mRNA in the locus coeruleus in the 6-OHDA-lesioned rat model of Parkinson's disease. In addition, the data show that repeated treatment with l-DOPA in 6-OHDA-lesioned rats, which induces dyskinesia, restores alpha(2A) mRNA levels. These changes of alpha(2A) mRNA expression, observed in the locus coeruleus, might be of importance to basal ganglia transmission and motor function.
引用
收藏
页码:145 / 152
页数:8
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