Mr. Zarrindast et al., Involvement of adrenergic and cholinergic systems in nicotine-induced anxiogenesis in mice, EUR J PHARM, 407(1-2), 2000, pp. 145-158
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.