Involvement of adrenergic and cholinergic systems in nicotine-induced anxiogenesis in mice

In the present study, the effect of alpha -adrenoceptor agents on response to nicotine in an anxiety model (elevated plus-maze) in mice was investigat ed. Administered nicotine reduced indices of anti-anxiety behaviour (percen t open-arm time (%open-arm time) and percent open-arm entries (%open-arm en try)) and increased indices of anxiety behaviour (protected stretched atten tion posture and percent of protected head dipping (%protected dipping)), i ndicating that nicotine elicits an anxiogenic response. This response to th e drug was obtained 7 min but not 30 min after drug injection and with dose s of 0.25 and 0.5 mg/kg. Nicotinic receptor antagonists mecamylamine (0.5 a nd 1 mg/kg) and hexamethonium (5 and 10 mg/kg) reduced the response induced by nicotine (0.25 mg/kg). Mecamylamine (1 mg/kg; decreased %open-arm entry and increased protected stretched attention posture) and hexamethonium (10 mg/kg; decreased %open-arm time) showed an anxiogenic-like profile. A musc arinic receptor antagonist, atropine (2.5 and 5 mg/kg), did not alter the n icotine response but elicited an anxiogenic effect by itself. The alpha (1) -adrenoceptor antagonist prazosin (0.25 and 0.5 mg/kg), but not the alpha ( 1)-adrenoceptor agonist, phenylephrine (4 and 6 mg/kg), reversed the nicoti ne effect. Single administration of phenylephrine (6 mg/kg) increased %open -arm time, while prazosin did not alter the anxiety behaviour. The alpha (2 )-adrenoceptor agonist clonidine (0.001 and 0.01 mg/kg), induced complete i mmobility when administered in combination with nicotine. However, an alpha (2)-adrenoceptor antagonist, yohimbine (0.5 and 1 mg/kg), appeared to reve rse the nicotine response, but did not show interaction with nicotine's eff ect. Clonidine did not elicit any effect, but yohimbine (1 mg/kg) increased %open-arm entry and %open-arm time by itself. It can be concluded that cer tain doses of nicotine (0.25 and 0.5 mg/kg) 7 min after their injection ind uce an anxiogenic effect through nicotinic mechanism(s), and that involveme nt of alpha (1)- but not alpha (2)-adrenoceptors in the response to nicotin e seems likely. (C) 2000 Elsevier Science B.V. All rights reserved.