McFadden Lisa M, Vieira-Brock Paula L, Hanson Glen R, Fleckenstein Annette E
Department of Pharmacology and Toxicology,University of Utah,Salt Lake City, UT 84112,USA.
Int J Neuropsychopharmacol. 2014 Aug;17(8):1315-20. doi: 10.1017/S1461145714000327. Epub 2014 Mar 20.
Preclinical studies suggest that prior treatment with escalating doses of methamphetamine (METH) attenuates the persistent deficits in hippocampal serotonin (5-hydroxytryptamine; 5HT) transporter (SERT) function resulting from a subsequent 'binge' METH exposure. Previous work also demonstrates that brain-derived neurotrophic factor (BDNF) exposure increases SERT function. The current study investigated changes in hippocampal BDNF protein and SERT function in rats exposed to saline or METH self-administration prior to a binge exposure to METH or saline. Results revealed that METH self-administration increased hippocampal mature BDNF (mBDNF) immunoreactivity compared to saline-treated rats as assessed 24 h after the start of the last session. Further, mBDNF immunoreactivity was increased and SERT function was not altered in rats that self-administered METH prior to the binge METH exposure as assessed 24 h after the binge exposure. These results suggest that prior exposure to contingent METH increases hippocampal mBDNF, and this may contribute to attenuated deficits in SERT function.
临床前研究表明，先用递增剂量的甲基苯丙胺（METH）进行治疗，可减轻随后“暴饮暴食”式METH暴露导致的海马5-羟色胺（5-HT）转运体（SERT）功能的持续性缺陷。先前的研究还表明，脑源性神经营养因子（BDNF）暴露可增强SERT功能。本研究调查了在暴饮暴食式暴露于METH或生理盐水之前，暴露于生理盐水或自行给药METH的大鼠海马BDNF蛋白和SERT功能的变化。结果显示，与生理盐水处理的大鼠相比，在最后一次给药开始24小时后评估发现，自行给药METH可增加海马成熟BDNF（mBDNF）免疫反应性。此外，在暴饮暴食式暴露于METH后24小时评估发现，在暴饮暴食式暴露于METH之前自行给药METH的大鼠，其mBDNF免疫反应性增加，而SERT功能未改变。这些结果表明，先前接触间歇性METH会增加海马mBDNF，这可能有助于减轻SERT功能的缺陷。
