Department of Psychiatry, UW-Madison, Madison, WI, USA.
Psychopharmacology (Berl). 2012 Apr;220(3):465-79. doi: 10.1007/s00213-011-2490-2. Epub 2011 Sep 23.
Prepulse inhibition (PPI), a preattentional information-filtering mechanism, is disrupted by serotonin (5-HT) or norepinephrine (NE) agonists to model deficits seen in schizophrenia, but whether this effect occurs through interactions between these systems is not known.
These studies investigated whether PPI/activity changes induced by agonists of one system were dependent on neurotransmission within the other.
Male Sprague-Dawley rats received the 5-HT(2) receptor agonist DOI (1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane) (0, 0.3 mg/kg), with or without antagonists for α1 (prazosin:0, 0.3, or 1 mg/kg) or β (timolol:0, 3, or 10 mg/kg) receptors or their combination (0 or 0.3 mg/kg prazosin + 3 mg/kg timolol), or the 5-HT(2) antagonist ritanserin (0, 2 mg/kg). Separately, the α1-adrenergic receptor agonist cirazoline (0, 0.68 mg/kg) was given with and without ritanserin (0, 0.5, or 2 mg/kg) or the NE antagonists (0 or 0.3 mg/kg prazosin + 3 mg/kg timolol). Finally, combinations of subthreshold doses of DOI (0, 0.01, 0.025 mg/kg) and cirazoline (0, 0.1, 0.25 mg/kg) were tested for their ability to disrupt PPI, and concomitant administration of all three antagonists (0 vs. 0.3 mg/kg prazosin + 3 mg/kg timolol + 2 mg/kg ritanserin) was assessed for its ability to modify PPI. Locomotion was assessed in an additional set of experiments.
Doses/combinations of prazosin and timolol that reversed cirazoline-induced effects did not alter DOI-induced effects, and ritanserin did not affect cirazoline at doses that blocked DOI-mediated effects. Concomitant antagonism of α1 + β + 5-HT(2) receptors did not modify PPI, nor did combinations of subthreshold doses of cirazoline and DOI.
5-HT(2) receptors and α1 and β NE receptors may act through independent mechanisms to modulate sensorimotor gating and locomotor activity.
前脉冲抑制（PPI）是一种前注意信息过滤机制，其可被 5-羟色胺（5-HT）或去甲肾上腺素（NE）激动剂破坏，以模拟精神分裂症中观察到的缺陷，但这种效应是否通过这些系统之间的相互作用发生尚不清楚。
这些研究旨在调查一种系统的激动剂引起的 PPI/活性变化是否依赖于另一种系统的神经传递。
雄性 Sprague-Dawley 大鼠接受 5-HT（2）受体激动剂 DOI（1-[2,5-二甲氧基-4-碘苯基]-2-氨基丙烷）（0、0.3mg/kg），并用或不使用 α1（哌唑嗪：0、0.3 或 1mg/kg）或β（噻洛尔：0、3 或 10mg/kg）受体拮抗剂或其组合（0 或 0.3mg/kg 哌唑嗪+3mg/kg 噻洛尔），或 5-HT（2）拮抗剂利坦色林（0、2mg/kg）。另外，α1-肾上腺素能受体激动剂可乐定（0、0.68mg/kg）与利坦色林（0、0.5 或 2mg/kg）或 NE 拮抗剂（0 或 0.3mg/kg 哌唑嗪+3mg/kg 噻洛尔）同时给予。最后，测试亚阈剂量 DOI（0、0.01、0.025mg/kg）和可乐定（0、0.1、0.25mg/kg）的组合对 PPI 的破坏能力，同时评估三种拮抗剂（0 与 0.3mg/kg 哌唑嗪+3mg/kg 噻洛尔+2mg/kg 利坦色林）对 PPI 的修饰能力。在另一组实验中评估了运动。
逆转可乐定诱导作用的哌唑嗪和噻洛尔剂量/组合不改变 DOI 诱导的作用，而利坦色林在阻断 DOI 介导的作用的剂量下不影响可乐定。同时拮抗 α1+β+5-HT（2）受体不改变 PPI，也不改变亚阈剂量可乐定和 DOI 的组合。
5-HT（2）受体和 α1 和β NE 受体可能通过独立的机制作用于调节感觉运动门控和运动活动。
