Electrolytic lesions of the locus coeruleus or 6-hydroxydopamine lesions of the medial forebrain bundle protect against excitotoxic damage in rat hippocampus

Arvin, B. Mak; Peillet, E. Le; Dürmüller, Niklaus; Chapman, A. Chaston; Meldrum, Brian S.

doi:10.1016/0006-8993(92)90061-d

Cited by 9 publications

(3 citation statements)

References 16 publications

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“…Finally, a significant Side × Lesion interaction was found upon analysis of DA (F 1,31 = 7.40, p<0.01) which indicated DA depletion was more pronounced on the side ipsilateral to DA + NE lesion (p<0.05). In the hippocampus, a region that receives direct innervation from the LC via the MFB (Arvin et al, 1992), main effects of Side (Intact vs. Lesion) were observed for DOPAC only (F 1,31 = 6.94, p<0.02) and post hoc analysis revealed a significant reduction in DOPAC ipsilateral to the lesion (p<0.05). Importantly, a main effect of lesion (DA vs. DA + NE) was also observed for hippocampal NE (F 1,31 = 12.08, p<0.002).…”

Section: Resultsmentioning

confidence: 99%

Effects of noradrenergic denervation on L-DOPA-induced dyskinesia and its treatment by α- and β-adrenergic receptor antagonists in hemiparkinsonian rats

Barnum

Bhide

Lindenbach

et al. 2012

Pharmacology Biochemistry and Behavior

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While L-3,4-dihydroxyphenylalanine (L-DOPA) remains the standard treatment for Parkinson’s disease (PD), long-term efficacy is often compromised by L-DOPA-induced dyskinesia (LID). Recent research suggests that targeting the noradrenergic (NE) system may provide relief from both PD and LID, however, most PD patients exhibit NE loss which may modify response to such strategies. Therefore this investigation aimed to characterize the development and expression of LID and the anti-dyskinetic potential of the α2- and β-adrenergic receptor antagonists idazoxan and propranolol, respectively, in rats receiving 6-OHDA lesions with (DA lesion) or without desipramaine protection (DA + NE lesion). Male Sprague–Dawley rats (N = 110) received unilateral 6-hydroxydopamine lesions. Fifty-three rats received desipramine to protect NE neurons (DA lesion) and 57 received no desipramine reducing striatal and hippocampal NE content 64% and 86% respectively. In experiment 1, the development and expression of L-DOPA-induced abnormal involuntary movements (AIMs) and rotations were examined. L-DOPA efficacy using the forepaw adjusting steps (FAS) test was also assessed in DA- and DA + NE-lesioned rats. In experiment 2, DA- and DA + NE-lesioned rats received pre-treatments of idazoxan or propranolol followed by L-DOPA after which the effects of these adrenergic compounds were observed. Results demonstrated that moderate NE loss reduced the development and expression of AIMs and rotations but not L-DOPA efficacy while anti-dyskinetic efficacy of α2- and β-adrenergic receptor blockade was maintained. These findings suggest that the NE system modulates LID and support the continued investigation of adrenergic compounds for the improved treatment of PD.

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Section: Resultsmentioning

confidence: 99%

Effects of noradrenergic denervation on L-DOPA-induced dyskinesia and its treatment by α- and β-adrenergic receptor antagonists in hemiparkinsonian rats

Barnum

Bhide

Lindenbach

et al. 2012

Pharmacology Biochemistry and Behavior

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“…30 Norepinephrine depletion is associated with better outcome after ischemic damage 31 and lesions of the locus ceruleus are associated with less hippocampal damage than the contralateral side without the lesion. 32 Thus, in patients with PD, the deficiency of neurotransmitters implicated in excitotoxic cell death may also have a role in our finding of decreased stroke in patients with PD. There are, however, no definitive studies to verify this.…”

Section: Figmentioning

confidence: 92%

Parkinson's disease, stroke, and related epidemiology

Nataraj

Rajput

2005

Movement Disorders

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We investigated the prevalence of cerebrovascular disease and other comorbidities in Parkinson's disease (PD) patients compared to the general population. Five hundred PD patients were chosen randomly from one author's (A.H.R.) database. Age- and sex-matched controls were derived from 270 patients with essential tremor from the same database and from 490 patients in a general practitioner's database. Age, hypertensive status, smoking status, coronary artery disease, orthostatic hypotension, diabetes mellitus, and symptomatic cerebrovascular disease (stroke or transient ischemic attack) were assessed. Statistical analysis was performed using Pearson chi(2) testing and binary logistic regression analysis. The prevalence of coronary artery disease, hypertension, diabetes mellitus, and orthostatic hypotension was similar among groups. The PD group had more patients who never smoked and less current smokers than the other groups. While there were similar frequencies of symptomatic cerebrovascular disease among groups, the prevalence of stroke was lower in PD patients. This difference disappeared upon stratification into groups based on smoking status and in the addition of smoking as a covariate in the multivariate analysis. Diminished smoking in PD patients likely plays a role in our finding of decreased stroke in patients with PD. Increased access to appropriate neurological care and subsequent prevention of stroke after a warning transient ischemic attack may also play a role, as may diminished levels of excitotoxic neurotransmitters in PD patients.

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“…Norepinephrine is more diffusely deficient in patients with PD, being deficient throughout the cortex 30. Norepinephrine depletion is associated with better outcome after ischemic damage31 and lesions of the locus ceruleus are associated with less hippocampal damage than the contralateral side without the lesion 32. Thus, in patients with PD, the deficiency of neurotransmitters implicated in excitotoxic cell death may also have a role in our finding of decreased stroke in patients with PD.…”

Section: Discussionmentioning

confidence: 97%

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Electrolytic lesions of the locus coeruleus or 6-hydroxydopamine lesions of the medial forebrain bundle protect against excitotoxic damage in rat hippocampus

Cited by 9 publications

References 16 publications

Effects of noradrenergic denervation on L-DOPA-induced dyskinesia and its treatment by α- and β-adrenergic receptor antagonists in hemiparkinsonian rats

Effects of noradrenergic denervation on L-DOPA-induced dyskinesia and its treatment by α- and β-adrenergic receptor antagonists in hemiparkinsonian rats

Parkinson's disease, stroke, and related epidemiology

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