Rauca C, Schröder H
Otto-von-Guericke University Magdeburg, Medical Faculty, Institute of Pharmacology and Toxicology, Germany.
Peptides. 1995;16(4):635-40. doi: 10.1016/0196-9781(95)00015-c.
Three behavioral models were used to characterize the pharmacological action of BCH 325 on central dopaminergic transmission. The effect of acute SC treatment with BCH 325 upon dopaminergic mechanisms affecting motor activity was studied on the climbing behavior of mice. It was shown that the beta-casomorphin analogue evoked a dose-dependent increase in apomorphine (APO)-induced hypoactivity that was reversed by sulpiride (SULP). In in vitro studies on slices of nucleus accumbens of mice it could be demonstrated that 10(-6) M APO caused a reduction of K(+)-stimulated [14C]dopamine (DA) release that was potentiated following simultaneous incubation with 10(-6) M BCH 325. To prove a postsynaptic influence in D1 receptor-mediated behavior pattern, the action of BCH 325 was studied on bromocriptine (BROMO)-evoked yawning behavior of rats after pretreatment with reserpine (RES) or saline. The peptide could not influence the BROMO yawning after saline administration, but it was able to normalize the number of yawns, which were reduced after RES. To investigate the effect of BCH 325 on postsynaptic D2 receptors, jerking behavior on RES-pretreated rats after a high dose of BROMO was used. Following RES pretreatment only, the number of BROMO-induced jerks was decreased by treatment of rats with 0.5 mumol/kg BCH 325. In contrast, the jerking behavior was enhanced by 0.5 mumol/kg BCH 325 in rats that were additionally treated with alpha-methyl-p-tyrosine (MPT). In biochemical studies on slices of the nucleus accumbens of mice, the in vivo pretreatment with RES caused a reduction of K(+)-stimulated [14C]DA release that was blocked by the SC administration of 0.5 mumol/kg BCH 325.(ABSTRACT TRUNCATED AT 250 WORDS)
采用三种行为学模型来表征BCH 325对中枢多巴胺能传递的药理作用。通过研究BCH 325急性皮下注射对影响小鼠运动活动的多巴胺能机制的作用,观察其对小鼠攀爬行为的影响。结果表明,β-酪蛋白吗啡类似物引起阿扑吗啡(APO)诱导的活动减退呈剂量依赖性增加,且这种增加可被舒必利(SULP)逆转。在对小鼠伏隔核切片的体外研究中发现,10⁻⁶ M APO可导致钾离子刺激的[¹⁴C]多巴胺(DA)释放减少,而与10⁻⁶ M BCH 325共同孵育后这种减少作用增强。为了证明对D1受体介导的行为模式存在突触后影响,在大鼠经利血平(RES)或生理盐水预处理后,研究BCH 325对溴隐亭(BROMO)诱发的打哈欠行为的作用。给予生理盐水后,该肽不影响BROMO诱发的打哈欠行为,但能使RES处理后减少的哈欠次数恢复正常。为了研究BCH 325对突触后D2受体的作用,采用高剂量BROMO处理RES预处理的大鼠后的抽搐行为进行研究。仅在RES预处理后,用0.5 μmol/kg BCH 325处理大鼠可减少BROMO诱导的抽搐次数。相反,在额外用α-甲基-对-酪氨酸(MPT)处理的大鼠中,0.5 μmol/kg BCH 325增强了抽搐行为。在对小鼠伏隔核切片的生化研究中,RES体内预处理导致钾离子刺激的[¹⁴C]DA释放减少,而皮下注射0.5 μmol/kg BCH 325可阻断这种减少。(摘要截选至250字)