Agonists at nicotinic acetylcholine receptors (nAChRs) constitute one drug class being evaluated as analgesics. Previous preclinical studies have implicated α4β2 and α7 nAChRs as potential mediators of the antinociceptive effects of nAChR agonists; however, these studies have relied exclusively on measures of pain-stimulated behavior. Pain is also associated with depression of many behaviors, and drug effects can differ in assays of pain-stimulated vs. pain-depressed behavior. This study compared effects of nicotine, the selective α4/6β2 agonist 5-I-A-85380, and the selective α7 agonist PNU 282987 in assays of pain-stimulated and pain-depressed behavior in rats. Nicotine produced a blockade of both acid-stimulated stretching and acid-induced depression of intracranial self-stimulation (ICSS). 5-I-A-85380 also blocked both acid-stimulated stretching and acid-induced depression of ICSS, whereas PNU 282987 produced no effect in either procedure. These results suggest that stimulation of α4β2 and/or α6β2 nAChRs may be effective to alleviate signs of pain-related behavioral depression in rats.
See article at J Pharmacol Exp Ther 2015, 355:341-350.
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