Ikeda Hiroko, Moribe Shoko, Sato Michiko, Kotani Ayako, Koshikawa Noriaki, Cools Alexander R
Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Eur J Pharmacol. 2007 Jan 12;554(2-3):175-82. doi: 10.1016/j.ejphar.2006.10.007. Epub 2006 Oct 17.
The role of alpha- and beta-adrenoceptors in the nucleus accumbens shell in turning behaviour of rats was investigated. Unilateral injections of the alpha-adrenoceptor agonist (phenylephrine; 10 microg) and antagonist (phentolamine; 10 microg) as well as the beta-adrenoceptor agonist (isoprenaline; 1 microg) and antagonist (propranolol; 5 microg) into the nucleus accumbens shell did not produce turning behaviour more than that of control vehicle injection. Unilateral injection of a mixture of dopamine D(1) ((+/-)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol, SKF 38393; 5 microg) and D(2) (quinpirole; 10 microg) receptor agonists into the nucleus accumbens shell has been found to elicit contraversive pivoting. Such pivoting was dose-dependently inhibited by phenylephrine (5, 10 microg), injected into the nucleus accumbens shell, and the inhibitory effect of phenylephrine (10 microg) was antagonised by phentolamine (10 microg) that per se had no effect on this pivoting. Isoprenaline (0.5, 1 microg) dose-dependently increased the contraversive pivoting induced by the mixture of SKF 38393 (1 microg) and quinpirole (10 microg) injected into the nucleus accumbens shell. The effect of isoprenaline (1 microg) was antagonised by propranolol (5 microg) that per se had no effect on this pivoting. It is concluded that stimulation of accumbal alpha-adrenoceptors inhibits the dopamine-dependent pivoting in contrast to stimulation of accumbal beta-adrenoceptors that facilitates this dopamine-dependent pivoting. Unilateral injection of the acetylcholine receptor agonist carbachol (5 microg) into the nucleus accumbens shell has been found to elicit contraversive circling. Such circling was significantly reduced by accumbal administration of either phenylephrine (10, 20 microg) or phentolamine (5, 10 microg) in a dose-independent manner; moreover, both drugs potentiated, but did not counteract, each other's effects. Carbachol-induced circling was also reduced by propranolol (2.5, 5 microg), but again in an aspecific manner. It is concluded that alpha- and beta-adrenergic agents have an effect on accumbal acetylcholine receptor-mediated circling through a non-adrenergic mechanism. The impact of the present study for putative new treatments of various neuropsychiatric and neurological disorders is discussed.
研究了伏隔核壳中α和β肾上腺素能受体在大鼠旋转行为中的作用。向伏隔核壳单侧注射α肾上腺素能受体激动剂(去氧肾上腺素;10微克)和拮抗剂(酚妥拉明;10微克)以及β肾上腺素能受体激动剂(异丙肾上腺素;1微克)和拮抗剂(普萘洛尔;5微克),所产生的旋转行为并不比注射对照赋形剂时更多。已发现向伏隔核壳单侧注射多巴胺D(1)((+/-)-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓-7,8-二醇,SKF 38393;5微克)和D(2)(喹吡罗;10微克)受体激动剂的混合物会引发反向旋转。这种旋转受到向伏隔核壳注射的去氧肾上腺素(5、10微克)的剂量依赖性抑制,而去氧肾上腺素(10微克)的抑制作用被酚妥拉明(10微克)拮抗,酚妥拉明本身对这种旋转没有影响。异丙肾上腺素(0.5、1微克)剂量依赖性地增加了向伏隔核壳注射SKF 38393(1微克)和喹吡罗(10微克)的混合物所诱导的反向旋转。异丙肾上腺素(1微克)的作用被普萘洛尔(5微克)拮抗,普萘洛尔本身对这种旋转没有影响。得出的结论是,与促进这种多巴胺依赖性旋转的伏隔核β肾上腺素能受体刺激相反,伏隔核α肾上腺素能受体的刺激抑制了多巴胺依赖性旋转。已发现向伏隔核壳单侧注射乙酰胆碱受体激动剂卡巴胆碱(5微克)会引发反向转圈。这种转圈被向伏隔核给予去氧肾上腺素(10、20微克)或酚妥拉明(5、10微克)以剂量非依赖性方式显著减少;此外,两种药物相互增强但不抵消彼此的作用。卡巴胆碱诱导的转圈也被普萘洛尔(2.5、5微克)减少,但同样是以非特异性方式。得出的结论是,α和β肾上腺素能药物通过非肾上腺素能机制对伏隔核乙酰胆碱受体介导的转圈有影响。讨论了本研究对各种神经精神和神经疾病假定新治疗方法的影响。