Peters S.L., Gray J.A., Joseph M.H.
MRC Brain, Behaviour and Psychiatry Research Group, Department of Psychology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK.
Behav Pharmacol. 1991 Jun;2(3):215-223.
Pre-weaning "handling" of rat pups (1-21 days) is reported to result in a number of behavioural differences from "nonhandled" pups, persisting into adult life. In general, these are associated with altered emotional reactivity. We now report the results of a replication of a previous finding that handling also affects performance on a latent inhibition (LI) task, which involves learning in the absence of motivation. The effect of 30 pre-exposures to a tone stimulus on the formation of an association from two pairings between that stimulus and footshock was determined. The association was indexed by the suppression of licking resulting from tone presentation during licking for water reward. In adult female rats, pre-exposure prevented the formation of this association (i.e. LI was present) whether they had been handled or nonhandled pre-weaning. However in adult males, pre-exposure was effective only in handled rats, and not in nonhandled. This confirms the striking pattern of results reported previously by another group (Weiner et al., 1987). The turnover of dopamine (DA) and serotonin was subsequently determined post mortem from the ratios of metabolites to amines in DA-innervated brain areas of the rats used in the present study. Pre-weaning nonhandling and female sex, were independently associated with increased dopamine turnover, and to a lesser extent with increased serotonin turnover. While these increases were not sex-specific, nonhandled males did show a pattern of increased DA turnover relative to serotonin turnover in limbic areas; previous pharmacological and physiological studies support the idea that this pattern may be associated with impairment of LI. It is concluded that preweaning nonhandling is indeed associated with an impairment of LI restricted to males, and is associated with enduring changes in DA and 5HT turnover in both sexes. Further studies are indicated to determine the precise role of these changes in the behavioural effects of pre-weaning nonhandling.
据报道,对幼鼠(1至21日龄)进行断奶前“处理”会导致其行为与“未处理”的幼鼠存在诸多差异,且这些差异会持续至成年期。一般来说,这些差异与情绪反应性的改变有关。我们现在报告一项重复先前研究结果的情况,即处理也会影响潜在抑制(LI)任务的表现,该任务涉及在无动机状态下的学习。研究确定了对音调刺激进行30次预暴露对该刺激与足部电击两次配对形成关联的影响。这种关联通过在舔舐获取水奖励期间音调呈现导致的舔舐抑制来衡量。在成年雌性大鼠中,无论断奶前是否经过处理,预暴露都能阻止这种关联的形成(即存在潜在抑制)。然而,在成年雄性大鼠中,预暴露仅对经过处理的大鼠有效,对未处理的大鼠无效。这证实了另一组(Weiner等人,1987年)先前报道的显著结果模式。随后,在本研究使用的大鼠多巴胺(DA)支配的脑区中,通过代谢物与胺的比率对死后的多巴胺和血清素周转率进行了测定。断奶前未处理和雌性性别分别与多巴胺周转率增加独立相关,在较小程度上也与血清素周转率增加相关。虽然这些增加并非性别特异性,但未处理的雄性大鼠在边缘区域确实表现出多巴胺周转率相对于血清素周转率增加的模式;先前的药理学和生理学研究支持这种模式可能与潜在抑制受损有关的观点。研究得出结论,断奶前未处理确实与仅限于雄性的潜在抑制受损有关,并且与两性中多巴胺和5-羟色胺周转率的持久变化有关。需要进一步研究以确定这些变化在断奶前未处理的行为影响中的精确作用。