Multiple spinal mediators in parenteral nicotine-induced antinociception.
The role of spinal mechanisms in subcutaneous (s.c.) nicotine-induced antinociception was examined in male Sprague-Dawley rats using the hot-plate and tail-flick tests. Nicotine (0.125, 0.25, 0.375 or 0.5 mg/kg s.c.) produced a dose-related inhibition of nociception in both tests. Although increasing negative geotaxis response times slightly, no significant alteration of other motor reflexes was observed with 0.375 mg/kg of s.c. nicotine. Microinjection of 7 nmol of the high-affinity choline uptake inhibitor hemicholinium-3 into the rostral ventral medulla completely inhibited the antinociception produced by 0.375 mg/kg of s.c. nicotine. Intrathecal (i.t.) injection of 61 nmol of nicotine (in 10 microliter buffer) produced no changes in hot-plate or tail-flick test response latencies. Nicotine-induced antinociception was blocked by a variety of i.t. antagonists injected 12 min before s.c. injection of 0.375 mg/kg of nicotine. In both tests, i.t. pretreatment with 0.1 mumol (in 10 microliter buffer) of scopolamine, methysergide, yohimbine, idazoxan, mecamylamine or 0.2 mumol of atropine attenuated nicotine-induced increases in test response latencies. Pretreatment with 0.1 mumol of atropine attenuated nicotine-induced increases in tail-flick test, but not in the hot-plate test. Pretreatment with 0.1 mumol of i.t. prazosin or naloxone produced no changes in nicotine-induced increases in test response latencies in either test. These data suggest that the antinociception produced by s.c. nicotine is mediated via a number of sites in the spinal cord, including alpha-2 adrenergic, serotonergic and muscarinic cholinergic.(ABSTRACT TRUNCATED AT 250 WORDS)
Rogers
D T
DT
Department of Pharmacology, University of Kentucky College of Medicine, Lexington.
Iwamoto
E T
ET
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D006426:Hemicholinium 3 / Q000494:pharmacology; D007275:Injections, Intravenous; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage*; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D006426:Hemicholinium 3; D009538:Nicotine; D009020:Morphine; D001285:Atropine; D012601:Scopolamine