Nicotine attenuates naloxone-induced jumping behaviour in morphine-dependent mice.

In the present study the effect of nicotine on naloxone-induced jumping behaviour in morphine-dependent mice was examined. In addition, the modulatory role of dopaminergic, adrenergic and cholinergic mechanisms upon the effect of nicotine were investigated. Animals were rendered dependent on morphine by subcutaneous (s.c.) injections of morphine sulfate 3 times a day for 3 days, and jumping behaviour was induced by intraperitoneal (i.p.) administration of naloxone 2 h after the tenth injection of morphine sulfate on day 4. Nicotine (0.001-2 mg/kg s.c.) caused a significant decrease in withdrawal jumping behaviour in morphine-dependent mice. The effect of nicotine was blocked by the central nicotinic antagonist mecamylamine (0.01-0.1 mg/kg i.p.) but not by the peripheral nicotinic antagonist hexamethonium (0.01 and 0.1 mg/kg i.p.) nor the muscarinic receptor antagonist atropine (2.5-10 mg/kg i.p.). The dopamine receptor antagonist SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5- phenyl-1H-3-benzazepine-7-ol maleate) (0.01-0.5 mg/kg s.c.) reduced the response induced by nicotine. The dopamine receptor antagonist sulpiride (25 and 50 mg/kg s.c.) and the adrenoceptor antagonists phenoxybenzamine (5 and 10 mg/kg i.p.) and propranolol (5 and 10 mg/kg i.p.) were without an effect. The results indicate that the effect of nicotine on naloxone-induced jumping is mediated by central nicotinic receptors.