甘氨酸/N-甲基-D-天冬氨酸受体拮抗剂R-(+)-HA-966可阻断苯环利定和地佐环平（MK-801）在啮齿动物中诱导的中脑边缘多巴胺能系统的激活。

The glycine/NMDA receptor antagonist, R-(+)-HA-966, blocks activation of the mesolimbic dopaminergic system induced by phencyclidine and dizocilpine (MK-801) in rodents.

作者信息

Bristow L J, Hutson P H, Thorn L, Tricklebank M D

机构信息

Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex.

出版信息

Br J Pharmacol. 1993 Apr;108(4):1156-63. doi: 10.1111/j.1476-5381.1993.tb13520.x.

DOI:10.1111/j.1476-5381.1993.tb13520.x

PMID:8485625

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908143/

Abstract

The effects of the glycine/N-methyl-D-aspartate (NMDA) receptor antagonist, R-(+)-HA-966 on the neurochemical and behavioural responses to phencyclidine (PCP) and dizocilpine (MK-801) have been determined in rodents. 2. In rats, pretreatment with PCP (5 and 10 mg kg-1) or MK-801 (0.25 and 0.5 mg kg-1) dose-dependently stimulated dopamine turnover in nucleus accumbens, amygdala and medial prefrontal cortex, but had no effect in striatum. In contrast, pretreatment with (+)-HA-966 (10 and 30 mg kg-1) did not affect dopamine turnover in any brain region investigated. 3. Pretreatment with (+)-HA-966 (10 and 30 mg kg-1) significantly antagonized the stimulation of dopamine turnover induced by both PCP (10 mg kg-1) and MK-801 (0.5 mg kg-1) in rat nucleus accumbens, amygdala and medial prefrontal cortex. 4. Intracerebral dialysis studies in conscious rats demonstrated that systemic injection of PCP (10 mg kg-1) markedly stimulated dopamine release from the nucleus accumbens, an effect that was abolished by pretreatment with (+)-HA-966 (30 mg kg-1). 5. Pretreatment with PCP (3-30 mg kg-1) or MK-801 (0.1-1.6 mg kg-1) significantly increased locomotor activity in mice. In contrast, subcutaneous injection of (+)-HA-966 (10-100 mg kg-1) failed to stimulate activity. 6. Pretreatment with (+)-HA-966 (10 and 30 mg kg-1) dose-dependently antagonized both PCP (10 mg kg-1) and MK-801 (0.4 mg kg-1) induced hyperactivity in mice. 7. Blockade of PCP-induced hyperactivity by (+)-HA-966 is unlikely to be explained by the induction or potentiation of sedation/ataxia since PCP-induced rotarod deficits were not significantly different in mice pretreated with (+)-HA-966 (30 mg kg-1) or saline.8. The results demonstrate that (+ )-HA-966 antagonizes both the neurochemical and behavioural effects of PCP and MK-801, possibly through interactions at the glycine/NMDA receptor.

摘要

已在啮齿动物中确定了甘氨酸/N-甲基-D-天冬氨酸（NMDA）受体拮抗剂R-(+)-HA-966对苯环利定（PCP）和地佐环平（MK-801）的神经化学及行为反应的影响。2. 在大鼠中，用PCP（5和10 mg/kg）或MK-801（0.25和0.5 mg/kg）预处理可剂量依赖性地刺激伏隔核、杏仁核和内侧前额叶皮质中的多巴胺周转，但对纹状体无影响。相比之下，用(+)-HA-966（10和30 mg/kg）预处理对所研究的任何脑区中的多巴胺周转均无影响。3. 用(+)-HA-966（10和30 mg/kg）预处理可显著拮抗PCP（10 mg/kg）和MK-801（0.5 mg/kg）在大鼠伏隔核、杏仁核和内侧前额叶皮质中诱导的多巴胺周转刺激。4. 清醒大鼠的脑内透析研究表明，全身注射PCP（10 mg/kg）可显著刺激伏隔核中的多巴胺释放，而用(+)-HA-966（30 mg/kg）预处理可消除该效应。5. 用PCP（3 - 30 mg/kg）或MK-801（0.1 - 1.6 mg/kg）预处理可显著增加小鼠的运动活性。相比之下，皮下注射(+)-HA-966（10 - 100 mg/kg）未能刺激活性。6. 用(+)-HA-966（10和30 mg/kg）预处理可剂量依赖性地拮抗PCP（10 mg/kg）和MK-801（0.4 mg/kg）诱导的小鼠多动。7. (+)-HA-966对PCP诱导的多动的阻断不太可能由镇静/共济失调的诱导或增强来解释，因为在用(+)-HA-966（30 mg/kg）或生理盐水预处理的小鼠中，PCP诱导的转棒试验缺陷无显著差异。8. 结果表明，(+)-HA-966可能通过在甘氨酸/NMDA受体处的相互作用来拮抗PCP和MK-801的神经化学及行为效应。

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甘氨酸/N-甲基-D-天冬氨酸受体拮抗剂R-(+)-HA-966可阻断苯环利定和地佐环平（MK-801）在啮齿动物中诱导的中脑边缘多巴胺能系统的激活。

The glycine/NMDA receptor antagonist, R-(+)-HA-966, blocks activation of the mesolimbic dopaminergic system induced by phencyclidine and dizocilpine (MK-801) in rodents.

作者信息

Bristow L J, Hutson P H, Thorn L, Tricklebank M D

机构信息

Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex.

出版信息

Br J Pharmacol. 1993 Apr;108(4):1156-63. doi: 10.1111/j.1476-5381.1993.tb13520.x.

DOI:10.1111/j.1476-5381.1993.tb13520.x

PMID:8485625

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908143/

Abstract

The effects of the glycine/N-methyl-D-aspartate (NMDA) receptor antagonist, R-(+)-HA-966 on the neurochemical and behavioural responses to phencyclidine (PCP) and dizocilpine (MK-801) have been determined in rodents. 2. In rats, pretreatment with PCP (5 and 10 mg kg-1) or MK-801 (0.25 and 0.5 mg kg-1) dose-dependently stimulated dopamine turnover in nucleus accumbens, amygdala and medial prefrontal cortex, but had no effect in striatum. In contrast, pretreatment with (+)-HA-966 (10 and 30 mg kg-1) did not affect dopamine turnover in any brain region investigated. 3. Pretreatment with (+)-HA-966 (10 and 30 mg kg-1) significantly antagonized the stimulation of dopamine turnover induced by both PCP (10 mg kg-1) and MK-801 (0.5 mg kg-1) in rat nucleus accumbens, amygdala and medial prefrontal cortex. 4. Intracerebral dialysis studies in conscious rats demonstrated that systemic injection of PCP (10 mg kg-1) markedly stimulated dopamine release from the nucleus accumbens, an effect that was abolished by pretreatment with (+)-HA-966 (30 mg kg-1). 5. Pretreatment with PCP (3-30 mg kg-1) or MK-801 (0.1-1.6 mg kg-1) significantly increased locomotor activity in mice. In contrast, subcutaneous injection of (+)-HA-966 (10-100 mg kg-1) failed to stimulate activity. 6. Pretreatment with (+)-HA-966 (10 and 30 mg kg-1) dose-dependently antagonized both PCP (10 mg kg-1) and MK-801 (0.4 mg kg-1) induced hyperactivity in mice. 7. Blockade of PCP-induced hyperactivity by (+)-HA-966 is unlikely to be explained by the induction or potentiation of sedation/ataxia since PCP-induced rotarod deficits were not significantly different in mice pretreated with (+)-HA-966 (30 mg kg-1) or saline.8. The results demonstrate that (+ )-HA-966 antagonizes both the neurochemical and behavioural effects of PCP and MK-801, possibly through interactions at the glycine/NMDA receptor.

摘要

已在啮齿动物中确定了甘氨酸/N-甲基-D-天冬氨酸（NMDA）受体拮抗剂R-(+)-HA-966对苯环利定（PCP）和地佐环平（MK-801）的神经化学及行为反应的影响。2. 在大鼠中，用PCP（5和10 mg/kg）或MK-801（0.25和0.5 mg/kg）预处理可剂量依赖性地刺激伏隔核、杏仁核和内侧前额叶皮质中的多巴胺周转，但对纹状体无影响。相比之下，用(+)-HA-966（10和30 mg/kg）预处理对所研究的任何脑区中的多巴胺周转均无影响。3. 用(+)-HA-966（10和30 mg/kg）预处理可显著拮抗PCP（10 mg/kg）和MK-801（0.5 mg/kg）在大鼠伏隔核、杏仁核和内侧前额叶皮质中诱导的多巴胺周转刺激。4. 清醒大鼠的脑内透析研究表明，全身注射PCP（10 mg/kg）可显著刺激伏隔核中的多巴胺释放，而用(+)-HA-966（30 mg/kg）预处理可消除该效应。5. 用PCP（3 - 30 mg/kg）或MK-801（0.1 - 1.6 mg/kg）预处理可显著增加小鼠的运动活性。相比之下，皮下注射(+)-HA-966（10 - 100 mg/kg）未能刺激活性。6. 用(+)-HA-966（10和30 mg/kg）预处理可剂量依赖性地拮抗PCP（10 mg/kg）和MK-801（0.4 mg/kg）诱导的小鼠多动。7. (+)-HA-966对PCP诱导的多动的阻断不太可能由镇静/共济失调的诱导或增强来解释，因为在用(+)-HA-966（30 mg/kg）或生理盐水预处理的小鼠中，PCP诱导的转棒试验缺陷无显著差异。8. 结果表明，(+)-HA-966可能通过在甘氨酸/NMDA受体处的相互作用来拮抗PCP和MK-801的神经化学及行为效应。

甘氨酸/N-甲基-D-天冬氨酸受体拮抗剂R-(+)-HA-966可阻断苯环利定和地佐环平（MK-801）在啮齿动物中诱导的中脑边缘多巴胺能系统的激活。

The glycine/NMDA receptor antagonist, R-(+)-HA-966, blocks activation of the mesolimbic dopaminergic system induced by phencyclidine and dizocilpine (MK-801) in rodents.

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甘氨酸/N-甲基-D-天冬氨酸受体拮抗剂R-(+)-HA-966可阻断苯环利定和地佐环平（MK-801）在啮齿动物中诱导的中脑边缘多巴胺能系统的激活。

The glycine/NMDA receptor antagonist, R-(+)-HA-966, blocks activation of the mesolimbic dopaminergic system induced by phencyclidine and dizocilpine (MK-801) in rodents.

作者信息

机构信息

出版信息