Mutual independence of 5-HT(2) and α1 noradrenergic receptors in mediating deficits in sensorimotor gating.
Mutual independence of 5-HT(2) and α1 noradrenergic receptors in mediating deficits in sensorimotor gating.
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DOI：
10.1007/s00213-011-2490-2
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发表时间：
2012-04
影响因子：
3.4
通讯作者：
Bakshi, Vaishali P
中科院分区：
文献类型：
--
作者：
Baisley, Sarah K;Fallace, Katherine L;Rajbhandari, Abha K;Bakshi, Vaishali P
前脉冲抑制（PPI），一种前注意信息过滤机制，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出现的缺陷，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。这些研究调查了一个系统的激动剂诱导的PPI/活性变化是否依赖于另一个系统内的神经传递。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、0.3 mg/kg），联合或不联合α1（哌唑嗪：0、0.3或1 mg/kg）或β（噻吗洛尔：0、3或10 mg/kg）受体拮抗剂或其组合（哌唑嗪0或0.3 mg/kg+噻吗洛尔3 mg/kg），或5-HT 2拮抗剂利坦色林（0、2 mg/kg）。单独给予α1-肾上腺素能受体激动剂环唑啉（0、0.68 mg/kg），同时给予和不给予利坦色林（0、0.5或2 mg/kg）或NE拮抗剂（0或0.3 mg/kg哌唑嗪+ 3 mg/kg噻吗洛尔）。最后，测试DOI（0、0.01、0.025 mg/kg）和环唑啉（0、0.1、0.25 mg/kg）的阈下剂量的组合破坏PPI的能力，并评估所有三种拮抗剂（0 vs. 0.3 mg/kg哌唑嗪+ 3 mg/kg噻吗洛尔+ 2 mg/kg利坦色林）的伴随施用改变PPI的能力。在另外一组实验中评估运动。逆转环唑啉诱导效应的哌唑嗪和噻吗洛尔的剂量/组合并未改变DOI诱导效应，并且在阻断DOI介导效应的剂量下，利坦色林并未影响环唑啉。α1+β+5-HT 2受体的同时拮抗作用不会改变PPI，阈下剂量的cirazoline和DOI的组合也不会改变PPI。5-HT 2受体、α1和β NE受体可能通过独立的机制调节感觉运动门控和运动活动。
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-HT2 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-HT2 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-HT2 receptors did not modify PPI, nor did combinations of subthreshold doses of cirazoline and DOI. 5-HT2 receptors and α1 and β NE receptors may act through independent mechanisms to modulate sensorimotor gating and locomotor activity.