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 investigated. Administered nicotine reduced indices of anti-anxiety behaviour (percent open-arm time (%open-arm time) and percent open-arm entries (%open-arm entry)) and increased indices of anxiety behaviour (protected stretched attention posture and percent of protected head dipping (%protected dipping)), indicating that nicotine elicits an anxiogenic response. This response to the drug was obtained 7 min but not 30 min after drug injection and with doses of 0.25 and 0.5 mg/kg. Nicotinic receptor antagonists mecamylamine (0.5 and 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 muscarinic receptor antagonist, atropine (2.5 and 5 mg/kg), did not alter the nicotine 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 nicotine 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 immobility when administered in combination with nicotine. However, an alpha(2)-adrenoceptor antagonist, yohimbine (0.5 and 1 mg/kg), appeared to reverse the nicotine response, but did not show interaction with nicotine's effect. 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 certain doses of nicotine (0.25 and 0.5 mg/kg) 7 min after their injection induce an anxiogenic effect through nicotinic mechanism(s), and that involvement of alpha(1)- but not alpha(2)-adrenoceptors in the response to nicotine seems likely.
Zarrindast
M R
MR
Department of Pharmacology, Medical School, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
Homayoun
H
H
Babaie
A
A
Etminani
A
A
Gharib
B
B
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy; D001285:Atropine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D015016:Yohimbine; D018738:Hexamethonium; D008464:Mecamylamine; D009538:Nicotine; D001285:Atropine; D003000:Clonidine; D011224:Prazosin