Hypothalamic-locus coeruleus mechanisms in the pathophysiology of "on-off" in L-dopa treated Parkinson's disease: a hypothesis.
Fluctuations in motor performance remain a major problem in the longterm management of Parkinson's disease (PD) patients. Although alterations in striatal dopaminergic activity have been initially thought to induce these complications, recent studies failed to support a major role for impaired dopaminergic neuronal or receptor functions in the pathogenesis of the on-off phenomenon. In the following I discuss the possibility that alterations in the activity of norepinephrinergic neurons at the level of the locus coeruleus (LC) associated with dysregulation of descending endorphinergic projections from the arcuate nucleus of the hypothalamus may be intimately involved in the pathogenesis of motor fluctuations in L-dopa treated PD.
Sandyk
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D000818:Animals; D004723:Endorphins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology*; D007980:Levodopa / Q000627:therapeutic use*; D008125:Locus Coeruleus / Q000378:metabolism / Q000503:physiopathology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*
D004723:Endorphins; D007980:Levodopa