Sams-Dodd F.
Pharmacological Research, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
Behav Pharmacol. 1995 Jan;6(1):55-65.
d-Amphetamine and phencyclidine (PCP) can induce a model psychosis in humans that resembles schizophrenia. Both drugs reproduce the positive symptoms of schizophrenia, but apparently only PCP mimics the negative symptoms. The purpose of this study was to determine the pharmacological profiles of d-amphetamine and PCP in the social interaction test, and to determine if they have disruptive effects on social behaviour in rats that may be comparable to the social isolation characteristic of negative symptoms. Acute and subchronic (daily for 5 days) administration of d-amphetamine (0.7-22µmol/kg) produced stereotyped behaviour at dosages of 10.4µmol/kg and upwards without any consistent effects on social behaviour. In contrast, acute and subchronic PCP (0.9-29µmol/kg) produced dose-dependent increases in stereotyped behaviour and ataxia as well as dose-dependent reductions in the social behaviour at dosages of 3.6µmol/kg and upwards. Thus, d-amphetamine and PCP had distinct effects on the social behaviour of rats. Both drugs produced stereotyped behaviour and locomotor hyperactivity, but only PCP dose-dependently disrupted social behaviour. This raises the possibility that PCP-induced social isolation in rats corresponds to the social isolation reported in humans under the influence of PCP, and that it can be used as an animal model of negative symptoms.
右旋苯丙胺和苯环利定(PCP)可在人类中诱发一种类似精神分裂症的模型性精神病。两种药物都会重现精神分裂症的阳性症状,但显然只有PCP能模拟阴性症状。本研究的目的是确定右旋苯丙胺和PCP在社会互动测试中的药理学特征,并确定它们对大鼠社会行为是否具有干扰作用,这种干扰作用可能与阴性症状的社会隔离特征相当。急性和亚慢性(连续5天每日给药)给予右旋苯丙胺(0.7 - 22µmol/kg),在剂量为10.4µmol/kg及以上时会产生刻板行为,而对社会行为没有任何一致的影响。相比之下,急性和亚慢性给予PCP(0.9 - 29µmol/kg)会使刻板行为和共济失调呈剂量依赖性增加,并且在剂量为3.6µmol/kg及以上时会使社会行为呈剂量依赖性减少。因此,右旋苯丙胺和PCP对大鼠的社会行为有不同的影响。两种药物都会产生刻板行为和运动活动亢进,但只有PCP会剂量依赖性地破坏社会行为。这就增加了一种可能性,即PCP诱导的大鼠社会隔离与人类在PCP影响下所报告的社会隔离相对应,并且它可以用作阴性症状的动物模型。