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Stimulus effects of d-amphetamine II: DA, NE, and 5-HT mechanisms.

机译:d-苯丙胺II的刺激作用:DA,NE和5-HT机制。

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摘要

Activation of dopaminergic (DA) systems is a necessary component of the behavior effects of d-amphetamine, but other neurotransmitters such as norepinephrine (NE) and serotonin (5-HT) appear to modulate DA input; thus, they might have an important role in the stimulus (subjective) effects of this drug. Therefore, rats were trained to discriminate d-amphetamine (1 mg/kg) from saline and given combination (antagonism, potentiation) or substitution (generalization) tests with drugs that act through DA, noradrenergic, or serotonergic (5-HT) mechanisms. In the first of two experiments, the D1 antagonist SCH 39166 blocked the effects of d-amphetamine (1 mg/kg) at doses of 0.05, 0.1, and 0.2 mg/kg. NE and 5-HT antagonists including prazosin (0.5-2 mg/kg), idazoxan (1.25-5 mg/kg), ketanserin (0.06-0.15 mg/kg), and metergoline (5-20 mg/kg) had no significant effects on the d-amphetamine cue. In the second experiment, neither the alpha 2-NE agonist clonidine (0.0025-0.1 mg/kg), the beta-NE agonist salbutamol (0.05-0.25 mg/kg), nor the NE uptake inhibitor nisoxetine (5-15 mg/kg) had d-amphetamine-like effects. The alpha 2-NE antagonist yohimbine (0.5-2 mg/kg) and the beta-NE antagonist propranolol (0.5-3 mg/kg) failed to alter the d-amphetamine cue. ICS 205-930 (10 mg/kg) neither mimicked nor blocked the effects of 1 mg/kg of d-amphetamine. Indeed, this 5-HT3 antagonist potentiated the actions of lower doses of d-amphetamine (0.25-0.4 mg/kg); the potentiation of the 0.25-mg/kg dose was blocked significantly by the alpha 1-NE antagonist prazosin (1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
机译:多巴胺能(DA)系统的激活是d-苯异丙胺行为影响的必要组成部分,但是其他神经递质(例如去甲肾上腺素(NE)和5-羟色胺(5-HT))似乎可以调节DA输入。因此,它们可能在这种药物的刺激(主观)作用中起重要作用。因此,训练大鼠以区分d-苯异丙胺(1 mg / kg)与盐水,并给予与通过DA,去甲肾上腺素或5-羟色胺能(5-HT)机制起作用的药物组合(拮抗,增强)或替代(泛化)测试。在两个实验的第一个实验中,D1拮抗剂SCH 39166以0.05、0.1和0.2 mg / kg的剂量阻断了d-苯丙胺(1 mg / kg)的作用。 NE和5-HT拮抗剂包括哌唑嗪(0.5-2 mg / kg),咪唑x吨(1.25-5 mg / kg),酮色林(0.06-0.15 mg / kg)和美特古琳(5-20​​ mg / kg)没有显着性对d-苯丙胺提示的影响。在第二个实验中,α2-NE激动剂可乐定(0.0025-0.1 mg / kg),β-NE激动剂沙丁胺醇(0.05-0.25 mg / kg)或NE摄取抑制剂尼西汀(5-15 mg / kg) )具有d-苯丙胺样作用。 α2-NE拮抗剂育亨宾(0.5-2 mg / kg)和β-NE拮抗剂普萘洛尔(0.5-3 mg / kg)无法改变d-苯丙胺的指示。 ICS 205-930(10 mg / kg)既不模拟也不阻断1 mg / kg d-苯异丙胺的作用。实际上,这种5-HT3拮抗剂增强了较低剂量的d-苯异丙胺(0.25-0.4 mg / kg)的作用。 α1-NE拮抗剂哌唑嗪(1 mg / kg)显着阻断了0.25 mg / kg剂量的增强作用。(摘要截断为250字)

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