Zarrindast M R, Homayoun H, Babaie A, Etminani A, Gharib B
Department of Pharmacology, Medical School, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
Eur J Pharmacol. 2000 Oct 27;407(1-2):145-58. doi: 10.1016/s0014-2999(00)00628-2.
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.
在本研究中，研究了α-肾上腺素能受体药物对小鼠焦虑模型（高架十字迷宫）中尼古丁反应的影响。给予尼古丁会降低抗焦虑行为指标（开放臂时间百分比（%开放臂时间）和开放臂进入百分比（%开放臂进入）），并增加焦虑行为指标（保护性伸展注意力姿势和保护性头部下垂百分比（%保护性下垂）），表明尼古丁会引发焦虑反应。在注射药物后7分钟而非30分钟时，以及使用0.25和0.5mg/kg剂量时，可观察到对该药物的这种反应。烟碱受体拮抗剂美加明（0.5和1mg/kg）和六甲铵（5和10mg/kg）可降低由尼古丁（0.25mg/kg）诱导的反应。美加明（1mg/kg；降低%开放臂进入并增加保护性伸展注意力姿势）和六甲铵（10mg/kg；降低%开放臂时间）表现出类似焦虑的特征。毒蕈碱受体拮抗剂阿托品（2.5和5mg/kg）未改变尼古丁反应，但自身引发了焦虑效应。α1-肾上腺素能受体拮抗剂哌唑嗪（0.25和0.5mg/kg）可逆转尼古丁效应，而α1-肾上腺素能受体激动剂去氧肾上腺素（4和6mg/kg）则不能。单次给予去氧肾上腺素（6mg/kg）可增加%开放臂时间，而哌唑嗪未改变焦虑行为。α2-肾上腺素能受体激动剂可乐定（0.001和0.01mg/kg）与尼古丁联合给药时会导致完全不动。然而，α2-肾上腺素能受体拮抗剂育亨宾（0.5和1mg/kg）似乎可逆转尼古丁反应，但未显示与尼古丁效应的相互作用。可乐定未引发任何效应，但育亨宾（1mg/kg）自身可增加%开放臂进入和%开放臂时间。可以得出结论，注射后7分钟时，某些剂量的尼古丁（0.25和0.5mg/kg）通过烟碱机制诱导焦虑效应，并且在对尼古丁的反应中似乎可能涉及α1-而非α2-肾上腺素能受体。
