Effects of nicotine on ambulatory activity in mice.
Nicotine (0.5 and 1.0 mg/kg) administered subcutaneously to mice decreased the ambulatory activity recorded by an ambulo-meter in a dose-dependent manner from 5 to 60 min after the administration, and the higher dose (1.0 mg/kg) caused a long-lasting ataxia. To be noted was the initial increment of ambulation which usually preceded the ataxia-inducing effect with every dose of nicotine, and the lowest dose (0.10 mg/kg) employed herein induced only the increasing effect on ambulation recorded for the first 20 min after its administration. The ataxia-inducing effect of nicotine (1.0 mg/kg) was attenuated by the pretreatment with mecamylamine (0.4-2.0 mg/kg) in a dose-dependent manner, though the attenuating effect waned at a higher dose (4.0 mg/kg). In contrast, pretreatment with either hexamethonium (2.5 and 5.0 mg/kg) or atropine (1.0, 2.5 and 5.0 mg/kg) did not affect the ataxia-inducing effect of nicotine. Atropine when administered alone was found to markedly increase the ambulatory activity at the doses used for the pretreatment. Measurement of the time-dependent change of [3H]-nicotine level in brain tissue after its subcutaneous injection revealed that there is a good correlation between the brain levels of the alkaloid and the intensity of its ataxic effect rather than the initial increasing effect on ambulation. The results obtained herein suggest that nicotine exerts its ataxic effect centrally, but the site and type of the receptor stimulated by nicotine remains to be identified.
Kita
T
T
Department of Pharmacology, Nara Medical University, Kashihara, Japan.
Nakashima
T
T
Shirase
M
M
Asahina
M
M
Kurogochi
Y
Y
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*
D006584:Hexamethonium Compounds; D008464:Mecamylamine; D009538:Nicotine; D001285:Atropine