Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy.
PLoS One. 2021 Jan 15;16(1):e0245559. doi: 10.1371/journal.pone.0245559. eCollection 2021.
We previously reported that treatment with the prototypical antidepressant imipramine induced a dose-dependent reduction of the ingestion of a 10% sucrose solution, due to reduction of the licking burst number, thus suggesting reduced motivation and/or increased satiation. Importantly, the experimental sessions were performed in an alternate order, either 1-h or 24-h after imipramine administration. The observation that imipramine effect was more pronounced in the "1-h after-treatment" sessions, i.e. at the time of the brain drug Cmax, led us to suggest that it was likely related to brain drug levels at testing time. However, such an experimental design does not allow to rule out the alternative possibility that the observed effect might be due to post-session administration, as previously observed with memantine. To determine whether imipramine-induced decrease of sucrose ingestion could be observed even in absence of post-session administration, we examined the effect of a daily 22 day treatment with imipramine (5, 10 and 20 mg/kg). In the first half of the treatment period all behavioural tests were performed 1-h after administration. In the second half of the treatment period, tests were performed alternatively either 1-h or 24-h after imipramine administration. The results confirm that imipramine reduces sucrose ingestion due to a reduction of the licking burst number. Most importantly, these results demonstrate that this effect does not require imipramine post-session administration, since it was present before the beginning of post-session administrations. This supports the interpretation of the reduction of sucrose ingestion as a consequence of reduced motivation and/or increased satiation. Thus, these findings, taken together with the results of our previous study, might be relevant in explaining the effects of imipramine in models of drug-seeking and in body weight gain reduction in rats, but not in accounting for the antidepressant therapeutic effect. At variance with the results of our previous study, an increase in burst size was present in the first half of the treatment period, which might be interpreted as a prohedonic effect and/or as a compensatory effect.
我们之前曾报道过，典型抗抑郁药丙咪嗪的治疗会导致 10%蔗糖溶液摄入的剂量依赖性减少，这是由于舔吸爆发次数的减少，从而表明动机降低和/或饱食感增加。重要的是，实验在交替的顺序中进行，要么在丙咪嗪给药后 1 小时，要么在 24 小时后。观察到丙咪嗪的作用在“治疗后 1 小时”的实验中更为明显，即在大脑药物 Cmax 时，这使我们认为它可能与测试时大脑药物水平有关。然而，这种实验设计并不能排除另一种可能性，即观察到的效应可能是由于给药后引起的，就像之前观察到的美金刚胺那样。为了确定即使没有给药后处理，是否仍能观察到丙咪嗪诱导的蔗糖摄入减少，我们检查了丙咪嗪（5、10 和 20 mg/kg）每日 22 天治疗的效果。在治疗期的前半部分，所有行为测试都在给药后 1 小时进行。在治疗期的后半部分，测试交替在丙咪嗪给药后 1 小时或 24 小时进行。结果证实，丙咪嗪通过减少舔吸爆发次数来减少蔗糖摄入。最重要的是，这些结果表明，这种效应不需要丙咪嗪给药后处理，因为它在给药后处理之前就存在。这支持了将蔗糖摄入减少解释为动机降低和/或饱食感增加的结果。因此，这些发现与我们之前的研究结果一起，可能与解释丙咪嗪在觅药模型中的作用以及在大鼠体重减轻中的作用有关，但与抗抑郁治疗效果无关。与我们之前的研究结果不同，在治疗期的前半部分出现了爆发大小的增加，这可能被解释为促进快感效应和/或补偿效应。
