Schijven D, Sousa V C, Roelofs J, Olivier B, Olivier J D A
Department of Women's and Children's Health, Uppsala University, Sweden.
Department of Clinical Neuroscience, Karolinska Institute, Sweden.
Pharmacol Biochem Behav. 2014 Jun;121:82-7. doi: 10.1016/j.pbb.2013.12.012. Epub 2013 Dec 15.
The Flinder Sensitive Line (FSL) is a rat strain that displays distinct behavioral and neurochemical features of major depression. Chronic selective serotonin reuptake inhibitors (SSRIs) are able to reverse these symptoms in FSL rats. It is well known that several abnormalities in the serotonergic system have been found in FSL rats, including increased 5-HT brain tissue levels and reduced 5-HT synthesis. SSRIs are known to exert (part of) their effects by desensitization of the 5-HT₁A receptor and FSL rats appear to have lower 5-HT1A receptor densities compared with Flinder Resistant Line (FRL) rats. We therefore studied the sensitivity of this receptor on the sexual behavior performance in both FRL and FSL rats. First, basal sexual performance was studied after saline treatment followed by treatment of two different doses of the 5-HT₁A receptor agonist ±8-OH-DPAT. Finally we measured the effect of a 5-HT₁A receptor antagonist to check for specificity of the 5-HT₁A receptor activation. Our results show that FSL rats have higher ejaculation frequencies compared with FRL rats which do not fit with a more depressive-like phenotype. Moreover FRL rats are more sensitive to effects of ±8-OH-DPAT upon EL and IF than FSL rats. The blunted response of FSL rats to the effects of ±8-OH-DPAT may be due to lower densities of 5-HT₁A receptors.
弗林德斯敏感品系（FSL）是一种大鼠品系，表现出重度抑郁症的明显行为和神经化学特征。慢性选择性5-羟色胺再摄取抑制剂（SSRIs）能够逆转FSL大鼠的这些症状。众所周知，在FSL大鼠中发现了5-羟色胺能系统的几种异常，包括脑组织中5-羟色胺（5-HT）水平升高和5-HT合成减少。已知SSRIs通过使5-HT₁A受体脱敏发挥（部分）作用，并且与弗林德斯抗性品系（FRL）大鼠相比，FSL大鼠似乎具有更低的5-HT₁A受体密度。因此，我们研究了该受体对FRL和FSL大鼠性行为表现的敏感性。首先，在生理盐水处理后，接着用两种不同剂量的5-HT₁A受体激动剂±8-羟基二丙胺基四氢萘（±8-OH-DPAT）处理，研究基础性行为表现。最后，我们测量了一种5-HT₁A受体拮抗剂的作用，以检查5-HT₁A受体激活的特异性。我们的结果表明，与FRL大鼠相比，FSL大鼠具有更高的射精频率，这与更类似抑郁的表型不符。此外，FRL大鼠对±8-OH-DPAT对射精潜伏期（EL）和插入频率（IF）的影响比FSL大鼠更敏感。FSL大鼠对±8-OH-DPAT作用的反应迟钝可能是由于5-HT₁A受体密度较低。
