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BACKGROUND: Intrathecally administered clonidine increases release of spinal acetylcholine, which may be related to its analgesic action in neuropathic pain. The current study determined the role of spinal muscarinic and nicotinic receptors in the antiallodynic effect of intrathecally administered clonidine in spinal nerve-ligated rats. METHODS: Allodynia was produced in rats by ligation of the left L5-L6 spinal nerves. Mechanical allodynia was determined by application of von Frey filaments to the left hindpaw. The effect of intrathecal injection of saline, two muscarinic receptor antagonists (atropine and scopolamine), and two nicotinic receptor antagonists (mecamylamine and hexamethonium) on the antiallodynic action produced by intrathecal administration of 20 microg clonidine was assessed in six groups of animals. Each group consisted of six to eight rats. RESULTS: Intrathecal injection of saline or muscarinic or nicotinic receptor antagonists did not alter the withdrawal thresholds. The antiallodynic effect produced by intrathecally administered clonidine was attenuated in a dose-dependent manner by intrathecal treatment with muscarinic and nicotinic antagonists. Although nicotinic receptor antagonists only partially attenuated the effect of clonidine, blockade of spinal muscarinic receptors almost abolished the antiallodynic effect of clonidine. CONCLUSIONS: These results demonstrate that the analgesic effect of intrathecally administered clonidine on neuropathic pain is mediated by spinal muscarinic and nicotinic receptors. Therefore, this study provides functional evidence that spinally released acetylcholine plays a role in the antiallodynic effect of intrathecally administered clonidine in neuropathic pain.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9952159&dopt=Abstract
J Gerontol A Biol Sci Med Sci. 1995 Mar;50(2):B90-6.
Effects of chlordiazepoxide and scopolamine, but not aging, on the detection and identification of conditional visual stimuli.
McGaughy J, Sarter M.
Department of Psychology, Ohio State University.
Our previous studies revealed impairments in the ability of aged rats to detect brief, rarely and unpredictably occurring stimuli. The failure of these impairments to interact with the effects of benzodiazepine receptor (BZR) ligands was attributed to low demands on stimulus-related information processing. Thus, in the present experiment, rats of different ages were trained to detect visual stimuli that were flashing at 20 Hz, or were constantly illuminated, for 8, 3, or 5 sec. Additionally, selection of the correct lever to report detection required the processing of propositional rules (e.g., flashing-go left; constant-go right), i.e., the identification of the stimulus. All measures of performance varied with stimulus duration. Subsedative doses of the BZR agonist chlordiazepoxide (CDP; 3.13, 4.69 mg/kg), similar to the effects of the muscarinic antagonist scopolamine (.025, 0.1 mg/kg), impaired response accuracy, increased the number of errors of omission and decreased response latencies. Animals aged 28 months omitted more trials following the administration of CDP than 12-month-old rats. Age did not produce main effects and did not interact with the effects of the drugs on response accuracy. It is speculated that, as stimuli had to be presented for relatively long periods of time (to maintain above chance-level discrimination performance), demands on detection remained too low to replicate previously documented effects of age. The demonstration of interactions between the effects of age and of BZR-ligands appears to depend on combined demands for stimulus detection and identification.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7874585&dopt=Abstract
Pharmacol Biochem Behav. 1976 Aug;5(2):157-63.
Scopolamine: effects on fear or defense responses in the rat.
Mollenauer S, Plotnik R, Southwick P.
In previous research scopolamine reduced fear or defense responses of rats to a cat, and removal of the rats' olfactory bulbs had the same effect. This suggested that scopolamine might have affected defense responses by blocking olfactory perception of the stimulus cat. The present experiments studied this possibility and explored further the effects of scopolamine on defense responses of the hooded rat. In Experiment 1 rats treated with scopolamine were found to be responsive to olfactory cues from a cat. When cat smell, but not a cat, was present in the apparatus, scopolamine-treated rats showed a large and significant suppression of food consumption. In Experiment 2 the effects of scopolamine on defense responses were shown to be generalizable to an inanimate stimulus, mechanical robot. Scopolamine caused significantly less freezing and avoidance and significantly shorter latencies to drink in the presence of the robot. One of the primary findings of the present research is that scopolamine has now been shown to reduce the defensive response of freezing in a variety of stimulus situations. This finding was thought to have important implications for the literature relating anticholinergic drugs and avoidance behavior.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=996050&dopt=Abstract
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