Attenuation of the effects of d-amphetamine on interval timing behavior by central 5-hydroxytryptamine depletion.
Attenuation of the effects of d-amphetamine on interval timing behavior by central 5-hydroxytryptamine depletion.
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DOI：
10.1007/s00213-008-1400-8
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发表时间：
2009-04
影响因子：
3.4
通讯作者：
Szabadi, E.
中科院分区：
文献类型：
--
作者：
Body, S.;Cheung, T. H. C.;Hampson, C. L.;den Boon, F. S.;Bezzina, G.;Fone, K. C. F.;Bradshaw, C. M.;Szabadi, E.
关键词：
在自由操作的心理物理过程中，间隔时间对单胺释放剂d-安非他明、D2样多巴胺受体激动剂喹吡罗和D1样激动剂6-氯-2，3，4，5-四氢-1-苯基-1H-3-苯并（SKF-81297）敏感。D-苯丙胺的作用可被选择性D1样受体和5-HT 2A受体拮抗剂所拮抗。目前尚不清楚d-苯丙胺的作用是否需要完整的5-羟色胺（5-HT）途径。本研究的目的是检查d-苯丙胺、喹吡罗和SKF-81297对完整大鼠和5-羟色胺能（5-HTergic）通路已消融大鼠中时间的影响。在自由操作的心理物理程序下训练大鼠在50秒的试验中按压杠杆A和B，其中在试验的前半部分间歇地提供强化以响应A，在试验的后半部分提供强化以响应B。在试验的连续5秒时间段中记录对B的响应百分比（%B）;将逻辑函数拟合到数据以推导定时指数（T50，对应于%B = 50%的时间; Weber分数）。d-苯丙胺（0.4 mg kg−1 i. p.）的作用，喹吡罗（0.08 mg kg-1 i. p.），和SKF-81297（0.4 mg kg−1 s.c.）比较了中缝核内注射5，7-二羟色胺破坏5-HTergic通路的大鼠和正常大鼠的脑组织中5-HTergic通路的变化。Quinpirole和SKF-81297降低了两组的T50; d-安非他明仅降低了假损伤组的T50。病变减少了80%的5-羟色胺水平，儿茶酚胺水平不受影响。d-安非他明对自由操作的心理物理过程中的表现的影响需要完整的5-HTergic系统。5-HT可能作用于5-HT 2A受体，在多巴胺释放中可能起“许可”作用。
Interval timing in the free-operant psychophysical procedure is sensitive to the monoamine-releasing agent d-amphetamine, the D2-like dopamine receptor agonist quinpirole, and the D1-like agonist 6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzepine (SKF-81297). The effect of d-amphetamine can be antagonized by selective D1-like and 5-HT2A receptor antagonists. It is not known whether d-amphetamine’s effect requires an intact 5-hydroxytryptamine (5-HT) pathway. The objective of this study was to examine the effects of d-amphetamine, quinpirole, and SKF-81297 on timing in intact rats and rats whose 5-hydroxytryptaminergic (5-HTergic) pathways had been ablated. Rats were trained under the free-operant psychophysical procedure to press levers A and B in 50-s trials in which reinforcement was provided intermittently for responding on A in the first half, and B in the second half of the trial. Percent responding on B (%B) was recorded in successive 5-s epochs of the trials; logistic functions were fitted to the data for derivation of timing indices (T50, time corresponding to %B = 50%; Weber fraction). The effects of d-amphetamine (0.4 mg kg−1 i.p.), quinpirole (0.08 mg kg−1 i.p.), and SKF-81297 (0.4 mg kg−1 s.c.) were compared between intact rats and rats whose 5-HTergic pathways had been destroyed by intra-raphe injection of 5,7-dihydroxytryptamine. Quinpirole and SKF-81297 reduced T50 in both groups; d-amphetamine reduced T50 only in the sham-lesioned group. The lesion reduced 5-HT levels by 80%; catecholamine levels were not affected. d-Amphetamine’s effect on performance in the free-operant psychophysical procedure requires an intact 5-HTergic system. 5-HT, possibly acting at 5-HT2A receptors, may play a ‘permissive’ role in dopamine release.
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影响因子：
1.3
作者：
Asgari, K;Body, S;Szabadi, E
通讯作者：
Szabadi, E
影响因子：
1.6
作者：
Body, S;Kheramin, S;Szabadi, E
通讯作者：
Szabadi, E
影响因子：
3.4
作者：
Body, S;Kheramin, S;Szabadi, E
通讯作者：
Szabadi, E
影响因子：
3.4
作者：
Cheung, THC;Bezzina, G;Szabadi, E
通讯作者：
Szabadi, E
影响因子：
3.4
作者：
Chiang, TJ;Al-Ruwaitea, ASA;Szabadi, E
通讯作者：
Szabadi, E