Ozcetin Ayse, Cevreli Burcu, Uzbay Tayfun
Uskudar University, Neuropsychopharmacology Application and Research Center (NPARC), Istanbul, Turkey.
Synapse. 2016 Dec;70(12):501-507. doi: 10.1002/syn.21923. Epub 2016 Jul 28.
Alpha-2 adrenergic receptors target several behavioral functions. These receptors may connect with the brain pathways mediating sensorimotor gating system that associate with psychoses, and the literature that investigate the relationship between alpha-2 receptors and sensorimotor gating system is very limited and some results are controversial. Thus, we aimed to investigate the role of alpha-2 receptors on prepulse inhibition (PPI) of acoustic startle reflex which is a measure of sensorimotor gating.
Adult male Wistar rats were subjects. PPI was measured as the per cent inhibition of the startle reflex produced by a startling pulse stimulus. The average PPI levels were used in the further analyses. Clonidine (0.03-1 mg/kg), an agonist of alpha-2 receptors, idazoxan (10 mg/kg), an antagonist alpha-2 receptors, and saline were injected to rats intraperitoneally. PPI was evaluated at two different startle intensity levels (78 and 86 dB, respectively).
Treatments produced some significant changes on PPI of startle reflex at all two levels of startle intensity. While clonidine (0.06, 0.25, 0.5, and 1 mg/kg) disrupted significantly PPI, idazoxan (10 mg/kg) did not produce any significant effect on PPI. However, pretreatment with idazoxan reversed significantly clonidine-induced disruption of PPI. Neither idazoxan (10 mg/kg) nor clonidine (1 mg/kg) produces any significant change on locomotor activity in naive rats.
Because idazoxan and clonidine also act through imidazoline receptors, our results suggest that alpha-2 and/or imidazoline receptors are associated with PPI of acoustic startle reflex in rats. Stimulation of these receptors may cause sensorimotor gating disturbances.
α-2肾上腺素能受体作用于多种行为功能。这些受体可能与介导感觉运动门控系统的脑通路相连，而该系统与精神病有关，且研究α-2受体与感觉运动门控系统之间关系的文献非常有限，一些结果也存在争议。因此，我们旨在研究α-2受体在听觉惊跳反射的前脉冲抑制（PPI）中的作用，PPI是感觉运动门控的一种测量指标。
成年雄性Wistar大鼠作为实验对象。PPI通过对由惊吓脉冲刺激产生的惊跳反射的抑制百分比来测量。进一步分析中使用平均PPI水平。将α-2受体激动剂可乐定（0.03 - 1毫克/千克）、α-2受体拮抗剂咪唑克生（10毫克/千克）和生理盐水腹腔注射给大鼠。在两个不同的惊跳强度水平（分别为78和86分贝）下评估PPI。
在两个惊跳强度水平下，各处理对惊跳反射的PPI均产生了一些显著变化。可乐定（0.06、0.25、0.5和1毫克/千克）显著破坏PPI，而咪唑克生（10毫克/千克）对PPI未产生任何显著影响。然而，用咪唑克生前处理可显著逆转可乐定诱导的PPI破坏。咪唑克生（10毫克/千克）和可乐定（1毫克/千克）对未处理大鼠的运动活性均未产生任何显著变化。
由于咪唑克生和可乐定也通过咪唑啉受体起作用，我们的结果表明α-2和/或咪唑啉受体与大鼠听觉惊跳反射的PPI相关。刺激这些受体可能导致感觉运动门控障碍。
