Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Medical Toxicology and Drug Abuse Research Center, Birjand University of Medical Sciences, Birjand, Iran; Rocky Mountain Poison and Drug Center, Denver, CO, USA.
Brain Res Bull. 2019 May;148:18-24. doi: 10.1016/j.brainresbull.2019.03.008. Epub 2019 Mar 20.
Methamphetamine (METH) relapse affects the function of the serotonergic system, which this system important for synaptic plasticity and brain-derived neurotrophic factor (BDNF) level. While there is a clear distribution of serotonin receptors in the reward and memory areas but the function of 5-HT receptor isn't known. This article assessed effects of BRL15572 hydrochloride (5-HT receptor antagonist) on behavior, long-term potentiation (LTP), and BDNF level in reinstated METH-rats. Conditioned place preference was induced by injecting METH (5 mg/kg; i.p.) or saline on the conditioning days. On the last day of extinction, they received priming METH [simultaneously with BRL (2 μg/5 μl; i.c.v.) or vehicle] or saline or saline + vehicle. Preference scores, LTP components and expression of BDNF were measured on the following day. The preference score of METH treatment increased dramatically more than the sham group and co-administration of BRL + METH couldn't decrease the preference score than the METH group. Also, METH treatment increased the population spike relative to the sham group, whereas the treatment METH + BRL attenuated this parameter than METH group. Furthermore, BDNF expression significantly increased in the METH group although it decreased markedly upon treatment with BRL. These results suggest that future studies should evaluate the potential of 5-HT antagonist for METH-reinstatement behaviors.
甲基苯丙胺(METH)复吸会影响 5-羟色胺能系统的功能,而该系统对突触可塑性和脑源性神经营养因子(BDNF)水平很重要。虽然 5-羟色胺受体在奖励和记忆区域有明确的分布,但 5-HT 受体的功能尚不清楚。本文评估了 BRL15572 盐酸盐(5-HT 受体拮抗剂)对复吸 METH 大鼠行为、长时程增强(LTP)和 BDNF 水平的影响。通过在条件化日给大鼠注射 METH(5mg/kg;ip)或生理盐水来诱导条件性位置偏好。在消退的最后一天,它们接受了引发 METH[同时给予 BRL(2μg/5μl;icv)或载体]或生理盐水或生理盐水+载体。在第二天测量偏好评分、LTP 成分和 BDNF 的表达。与假手术组相比,METH 处理组的偏好评分显著增加,而 BRL+METH 的联合给药并不能降低 METH 组的偏好评分。此外,与假手术组相比,METH 处理组的群体峰显著增加,而 METH+BRL 处理组则减弱了这一参数。此外,尽管 BRL 治疗后 BDNF 表达明显下降,但 METH 组的 BDNF 表达显著增加。这些结果表明,未来的研究应该评估 5-HT 拮抗剂对 METH 复吸行为的潜在作用。