A dystonia-like syndrome after neuropeptide (MSH/ACTH) stimulation of the rat locus ceruleus.
The movement disorder investigated in these studies has some features in common with human idiopathic dystonia, and information obtained in these studies may be of potential clinical benefit. The present experimental results indicated that peptidergic stimulation of the LC resulted in a NE-mediated inhibition of cerebellar Purkinje cells located at terminals of the ceruleo-cerebellar pathway. However, it is not certain as to the following: (a) what receptors were stimulated by the ACTH N-terminal fragments at the LC that resulted in this disorder; (b) whether NE, released onto Purkinje cell synapses located at terminals of the ceruleo-cerebellar pathway, did indeed cause the long-term depression at Purkinje cell synapses (previously described by others) that resulted in the long duration of the movement disorder; (c) whether the inhibition of inhibitory Purkinje cells resulted in disinhibition or increased excitability of the unilateral cerebellar fastigial or interpositus nuclei, the output targets of the Purkinje cell axons, that may have been an important contributing factor to this disorder. These questions are currently being investigated.
Jacquet
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Laboratory of Behavioral Neuropharmacology, Nathan Kline Institute, Orangeburg, New York 10962.
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004421:Dystonia / Q000139:chemically induced*; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D008781:Methyltyrosines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D013577:Syndrome; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D019805:alpha-Methyltyrosine; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D011433:Propranolol