neuropeptide-y and Muscle-Rigidity

The aim of this study was to evaluate the effects of centrally administered neuropeptide Y (NPY) on muscular rigidity induced by fentanyl in Sprague-Dawley rats. They were anesthetized with ketamine (120 mg/kg, i.p.) and their lungs were mechanically ventilated. Intravenous administration of fentanyl (100 microg/kg) consistently evoked a significant increase in the electromyographic activity (EMG) recorded from the sacrococcygeus dorsalis lateralis muscle. This implied muscular rigidity was appreciably attenuated by intracerebroventricular administration of NPY (4 nmol/2.5 microl). Microinjection of NPY (40 or 160 pmol/50 nl) into the bilateral locus coeruleus (LC) elicited an inhibition of the EMG activation induced by fentanyl in a dose-dependent manner. Microinjection of 160 pmol NPY plus antiserum against NPY (NPY(Ab), 1:20) into the LC failed to suppress fentanyl-induced muscular rigidity. However, this implied muscular rigidity was not affected by NPY plus normal rabbit serum (NRS, 1:20). In addition, NPY(Ab) or NRS per se had no substantial effect on the rigidity. Microinjection of NPY (160 pmol) into the areas adjacent to the LC did not attenuate the rigidity. Our results suggest that the centrally administered NPY attenuated fentanyl-induced muscular rigidity by acting at the LC, but endogenous NPY may not be involved in this process.

Topics: Animals; Cerebral Ventricles; Electromyography; Fentanyl; Injections, Intraventricular; Locus Coeruleus; Male; Microinjections; Muscle Rigidity; Muscle, Skeletal; Neuropeptide Y; Rabbits; Rats; Rats, Sprague-Dawley

Neuropeptide immunohistochemistry was used to test several hypotheses of the anatomical bases of chorea and rigidity-akinesia. To test the hypothesis that elevated concentration of striatal somatostatin causes chorea, we visually compared the density of striatal neurons containing somatostatin and neuropeptide Y in brains affected by choreic or rigid-akinetic Huntington's disease (HD). The density of these neurons was elevated in both rigid-akinetic and choreic HD specimens with an apparently normal total number of these neurons, indicating that elevated somatostatin concentration, by itself, does not lead to chorea. We tested the hypothesis that rigid-akinetic HD results from deficient dopaminergic nigrostriatal neurotransmission by examining tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra. In rigid-akinetic HD brains, there was no obvious reduction of nigral TH-IR neurons, indicating that rigid-akinetic HD is probably not due to loss of nigral dopaminergic neurons. Finally, we also examined the status of striatal projection neurons and found near total loss of all striatal neurons projecting to the lateral globus pallidus, medial globus pallidus, and substantia nigra in brains affected by rigid-akinetic HD in contrast to the preservation of neurons projecting to the medial globus pallidus in choreic HD. These results are consistent with the hypothesis that chorea results from preferential loss of striatal neurons projecting to the lateral globus pallidus and that rigid-akinetic HD is a consequence of the additional loss of striatal neurons projecting to the medial segment of the pallidum.

Topics: Adult; Child; Chorea; Corpus Striatum; Female; Globus Pallidus; Humans; Huntington Disease; Immunohistochemistry; Muscle Rigidity; Neural Pathways; Neuropeptide Y; Somatostatin; Substantia Nigra