0000000000241403
AUTHOR
Peter Jenner
Chronic l-DOPA treatment increases striatal cannabinoid CB1 receptor mRNA expression in 6-hydroxydopamine-lesioned rats
Abstract The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion of the left medial forebrain bundle and 3 weeks treatment with l -DOPA of normal and 6-OHDA lesioned rats on CB1r mRNA expression was investigated by in situ hybridization. A 6-OHDA lesion of nigrostriatal pathway alone, confirmed by the loss of nigral tyrosine hydroxylase mRNA, did not alter CB1r mRNA levels in the dopamine depleted striatum. Similarly, chronic l -DOPA treatment of normal rats had no effect on striatal CB1r mRNA expression. In contrast, chronic l -DOPA treatment of 6-OHDA-lesioned rats significantly increased CB1r mRNA expression in the denervated striatum. These results suggest that the CB1r activity ma…
Alterations in striatal neuropeptide mRNA produced by repeated administration of L-DOPA, ropinirole or bromocriptine correlate with dyskinesia induction in MPTP-treated common marmosets
Chronic administration of L-DOPA to MPTP-treated common marmosets induces marked dyskinesia while repeated administration of equivalent antiparkisonian doses of ropinirole and bromocriptine produces only mild involuntary movements. The occurrence of dyskinesia has been associated with an altered balance between the direct and indirect striatal output pathways. Using in situ hybridisation histochemistry, we now compare the effects of these drug treatments on striatal preproenkephalin-A (PPE-A) and adenosine A(2a) receptor mRNA expression as markers of the indirect pathway and striatal preprotachykinin (PPT) mRNA and preproenkephalin-B (PPE-B, prodynorphin) mRNA expression as markers of the d…
Increased neuropeptide Y mRNA expression in striatum in Parkinson's disease.
High levels of neuropeptide Y (NPY) are found in basal ganglia where it is co-localised with somatostatin (SOM) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH/d) in a population of striatal GABA containing interneurones. Although alterations occur in the levels of various neuropeptides in basal ganglia in Parkinson’s disease (PD), it is not known whether NPY is affected. Using in situ hybridisation immunohistochemistry, we have examined the distribution of NPY mRNA in the caudate nucleus, putamen and nucleus accumbens of normal individuals and patients with PD. NPY mRNA was weakly expressed in the caudate nucleus, putamen and nucleus accumbens in normal individuals with a…
6-Hydroxydopamine lesioning differentially affects α-synuclein mRNA expression in the nucleus accumbens, striatum and substantia nigra of adult rats
The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion and/or repeated administration of levodopa (L-DOPA) to normal and 6-OHDA-lesioned rats on alpha-synuclein mRNA expression was investigated by in situ hybridization histochemistry. A 6-OHDA lesion of the nigro-striatal pathway alone, confirmed by the loss of nigral tyrosine hydroxylase mRNA expression, markedly decreased alpha-synuclein mRNA in the lesioned substantia nigra (SN). In contrast, the levels of alpha-synuclein mRNA in the denervated striatum and nucleus accumbens were not altered. Chronic administration of L-DOPA to normal or 6-OHDA-lesioned rats had no effect on alpha-synuclein mRNA expression in the SN, striatum or nu…
Both Short- and Long-Acting D-1/D-2 Dopamine Agonists Induce Less Dyskinesia than l-DOPA in the MPTP-Lesioned Common Marmoset (Callithrix jacchus)
Abstract The current concept of dyskinesia is that pulsatile stimulation of D-1 or D-2 receptors by l -DOPA or short-acting dopamine agonists is more likely to induce dyskinesia compared to long-acting drugs producing more continuous receptor stimulation. We now investigate the ability of two mixed D-1/D-2 agonists, namely pergolide (long-acting) and apomorphine (short-acting), to induce dyskinesia in drug-naive MPTP-lesioned primates, compared to l -DOPA. Adult common marmosets ( Callithrix jacchus ) were lesioned with MPTP (2 mg/kg/day sc for 5 days) and subsequently treated with equieffective antiparkinsonian doses of l -DOPA, apomorphine, or pergolide for 28 days. l -DOPA, apomorphine, …
New Symptomatic Treatments for the Management of Motor and Nonmotor Symptoms of Parkinson's Disease
Motor symptoms are core features of Parkinson's disease, while nonmotor symptoms are present from the prodromal stage. Management strategies for the motor symptoms of Parkinson's disease have been widely researched and there have been many advances. Therapy has evolved from oral therapy to once a day to nonoral strategies, both for rescue and for infusion therapy. Treatment for nonmotor symptoms, however, has remained a key unmet need, although of late evidence base for management of some nonmotor symptoms such as pain, dementia, aspects of sleep dysfunction, and constipation has emerged. However, management of many nonmotor symptoms such as anxiety, apathy, fatigue, and insomnia remains un…