麦角酸二乙酰胺（LSD）和2-溴麦角酸二乙酰胺（2-溴LSD）对大鼠脱羧酶抑制后纹状体多巴积累的影响。

The effect of LSD and 2-bromo LSD on the striatal DOPA accumulation after decarboxylase inhibition in rats.

作者信息

Persson S A

出版信息

Eur J Pharmacol. 1977 May 1;43(1):73-83. doi: 10.1016/0014-2999(77)90162-5.

Abstract

LSD and BOL (0.125-0.5 mg/kg) were equipotent in increasing the in vivo tyrosine hydroxylation in the striatum as measured by the accumulation of DOPA after inhibition of neuronal decarboxylase. However, with 2--4 mg/kg doses, the maximum effect of BOL was larger than that of LSD. LSD and BOL antagonized the apomorphine-induced decrease of DOPA accumulation, without affecting the haloperidol-induced increase. LSD like apomorphine inhibited the increase of DOPA accumulation seen after reserpine, cerebral hemisection and after gamma-butyrolactone (GBL). The effect of apomorphine in rats given GBL was blocked by haloperidol, but not by BOL and promethazine, whereas that of LSD was inhibited by haloperidol, BOL, and promethazine. These findings suggest that LSD and BOL directly affect nigro-neostriatal dopamine neurons. LSD therefore appears to be a partial agonist and BOL a pure antagonist at dopamine autoreceptors. It is proposed in addition that LSD activates and BOL blocks 5-HT receptors that control DOPA formation.

摘要

通过抑制神经元脱羧酶后多巴（DOPA）的积累来衡量，麦角酸二乙酰胺（LSD）和勃地酮（BOL，0.125 - 0.5毫克/千克）在增加纹状体中体内酪氨酸羟化方面具有同等效力。然而，在2 - 4毫克/千克剂量下，BOL的最大效应大于LSD。LSD和BOL拮抗阿扑吗啡诱导的DOPA积累减少，而不影响氟哌啶醇诱导的增加。LSD与阿扑吗啡一样，抑制利血平、大脑半球切除术和γ-丁内酯（GBL）后所见的DOPA积累增加。氟哌啶醇可阻断给予GBL的大鼠中阿扑吗啡的作用，但BOL和异丙嗪不能阻断，而LSD的作用可被氟哌啶醇、BOL和异丙嗪抑制。这些发现表明，LSD和BOL直接影响黑质-新纹状体多巴胺神经元。因此，LSD似乎是多巴胺自身受体的部分激动剂，而BOL是纯拮抗剂。此外，有人提出LSD激活而BOL阻断控制DOPA形成的5-羟色胺受体。