Commissaris R L, Ardayfio P A, McQueen D A, Gilchrist G A, Overstreet D H
Department of Pharmaceutical Sciences, College of Pharmacy and AHP, Wayne State University, Detroit, MI 48202, USA.
Pharmacol Biochem Behav. 2000 Sep;67(1):199-205. doi: 10.1016/s0091-3057(00)00314-2.
The high DPAT sensitivity (HDS) and low DPAT sensitivity (LDS) rat lines are the result of selective breeding for differences in the hypothermic response to acute treatment with the 5-HT(1A) receptor agonist 8-hydroxydipropylaminotetralin (8-OHDPAT). The HDS rats exhibit a much greater hypothermic response than do the LDS rats. The present study examined conflict anxiety-like behavior and the effects of acute challenges with 8-OHDPAT and phenobarbital (PhB) on conflict behavior in HDS and LDS rats. Water-restricted (24-h deprivation) HDS and LDS rats were trained to drink from a tube that was occasionally electrified. The 5-s bouts of drinking tube electrification occurred on a fixed interval (FI) 30-s schedule and were signaled by the presence of a tone. Under this schedule, responding is suppressed approximately 10-fold during the tone-on periods compared to the no-tone periods. After two weeks of training in this repeated measures drink suppression conflict paradigm, the effects of acute challenges with 8-OHDPAT (30-500 microg/kg, SC, +10 min) or PhB (20 mg/kg, IP, +10 min) were determined. In control (i.e. , non-drug) conflict test sessions, rats of the HDS line accepted significantly fewer shocks than did rats of the LDS line. Acute treatment with 8-OHDPAT resulted in a modest increase in punished responding (maximum increase: +30-40 shocks/session) in both lines at doses of 60 and 125 microg/kg. Higher doses produced significant general behavioral disruption and substantial reductions in water intake (unpunished responding) in both HDS and LDS rats. Neither the increase in shocks received nor the decrease in water intake produced by these 8-OHDPAT challenges differed between HDS and LDS rats. In both lines, acute PhB treatment resulted in a more dramatic increase in punished responding than did 8-OHDPAT (+55-65 shocks/session) and an increase in water intake. The effects of PhB also did not differ between HDS and LDS rats. These data suggest that the HDS and LDS rats exhibit differences in baseline anxiety-like behavior in the conflict task, but do not differ in their response to acute challenges with PhB or 8-OHDPAT.
高DPAT敏感性（HDS）和低DPAT敏感性（LDS）大鼠品系是通过对5-羟色胺（1A）受体激动剂8-羟基二丙基氨基四氢萘（8-OHDPAT）急性治疗的体温过低反应差异进行选择性育种而产生的。HDS大鼠表现出比LDS大鼠更大的体温过低反应。本研究检查了冲突性焦虑样行为以及8-OHDPAT和苯巴比妥（PhB）急性刺激对HDS和LDS大鼠冲突行为的影响。对限水（24小时剥夺）的HDS和LDS大鼠进行训练，使其从偶尔会通电的管子中饮水。5秒的饮水管通电时段按固定间隔（FI）30秒的时间表进行，并由一个音调提示。在这个时间表下，与无音调时段相比，在音调开启时段反应被抑制约10倍。在这个重复测量饮水抑制冲突范式中训练两周后，确定了8-OHDPAT（30 - 500微克/千克，皮下注射，+10分钟）或PhB（20毫克/千克，腹腔注射，+10分钟）急性刺激的效果。在对照（即非药物）冲突测试时段，HDS品系的大鼠接受的电击明显少于LDS品系的大鼠。在60和125微克/千克剂量下，8-OHDPAT急性治疗导致两个品系的受罚反应适度增加（最大增加：+30 - 40次电击/时段）。更高剂量在HDS和LDS大鼠中均产生明显的一般行为扰乱和饮水量（未受罚反应）大幅减少。这些8-OHDPAT刺激所导致的接受电击增加或饮水量减少在HDS和LDS大鼠之间没有差异。在两个品系中，急性PhB治疗导致的受罚反应增加比8-OHDPAT更显著（+55 - 65次电击/时段），并且饮水量增加。PhB的效果在HDS和LDS大鼠之间也没有差异。这些数据表明，HDS和LDS大鼠在冲突任务中的基线焦虑样行为存在差异，但在对PhB或8-OHDPAT急性刺激的反应上没有差异。
