Ferrari F, Pelloni F, Giuliani D
Institute of Pharmacology, University of Modena, Italy.
Psychopharmacology (Berl). 1993;113(2):172-6. doi: 10.1007/BF02245694.
The behavioural effects induced in male Wistar rats by SND 919, a new drug reputed to have selective agonistic activity at D2 dopamine (DA) receptors, were studied. The following aspects of behaviour were considered: motor activity, stretching-yawning (SY), penile erection (PE) and stereotyped behaviour (SB). Intraperitoneal injection (IP) of the drug (0.01-20 mg/kg) induced an SY syndrome in the form of a bell-shaped dose-response curve, the effect being maximal at the dose of 0.1 mg/kg and disappearing completely at 10 mg/kg. SND 919 also potently elicited PE; this latter effect, however, was not coincident with SY induction, being maximal at 1 mg/kg and persisting at 10 and 20 mg/kg. SND 919-induced SY was potently antagonized by pretreatment not only with the D2 antagonist, L-sulpiride (20 mg/kg), but also with the alpha 2 antagonist, yohimbine (1, 3 mg/kg), and the more selective alpha 2 antagonist, idazoxan (1, 2 and 5 mg/kg). While sulpiride also decreased SND 919-induced PE, idazoxan at all doses and yohimbine at 1 mg/kg did not affect this behaviour. Inhibition of motor activity was induced by the D2 agonist at low doses (0.05, 0.1 mg/kg), while at high doses (1, 10 and 20 mg/kg), it was actually replaced by a form of SB characterized by downward sniffing and licking. When, for comparison, the D2 agonist, RU 24213 (0.1-20 mg/kg IP), was tested for PE, SY, motor activity and SB, it displayed a behavioural pattern very similar to that obtained with SND 919. Idazoxan (2 mg/kg), administered before RU 24213 (10 mg/kg), significantly antagonized the drug-induced SY, but not PE.(ABSTRACT TRUNCATED AT 250 WORDS)
对一种据称在D2多巴胺(DA)受体上具有选择性激动活性的新药SND 919在雄性Wistar大鼠中诱导的行为效应进行了研究。研究考虑了以下行为方面:运动活性、伸展-打哈欠(SY)、阴茎勃起(PE)和刻板行为(SB)。腹腔注射(IP)该药物(0.01 - 20毫克/千克)以钟形剂量-反应曲线的形式诱导出SY综合征,在0.1毫克/千克剂量时效应最大,在10毫克/千克时完全消失。SND 919也能有效引发PE;然而,后一种效应与SY诱导不一致,在1毫克/千克时最大,在10和20毫克/千克时持续存在。SND 919诱导的SY不仅被D2拮抗剂L-舒必利(20毫克/千克)预处理有效拮抗,也被α2拮抗剂育亨宾(1、3毫克/千克)以及更具选择性的α2拮抗剂伊达唑烷(1、2和5毫克/千克)拮抗。虽然舒必利也降低了SND 919诱导的PE,但所有剂量的伊达唑烷和1毫克/千克的育亨宾对这种行为没有影响。低剂量(0.05、0.1毫克/千克)的D2激动剂诱导运动活性受到抑制,而高剂量(1、10和20毫克/千克)时,它实际上被一种以向下嗅闻和舔舐为特征的SB形式所取代。为作比较,当测试D2激动剂RU 24213(0.1 - 20毫克/千克IP)的PE、SY、运动活性和SB时,它表现出与SND 919非常相似的行为模式。在RU 24213(10毫克/千克)之前给予伊达唑烷(2毫克/千克)可显著拮抗药物诱导的SY,但不影响PE。(摘要截断于250字)