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Putative Neurotoxicity of SKF 38393 and Other D 1 Dopaminergic Drugs Investigated in Rat Striatum
Author(s) -
Isaac L.,
Mills R.,
Fowler L. J.,
Starr B. S.,
Starr M. S.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb11365.x
Subject(s) - substantia nigra , striatum , agonist , dopaminergic , chemistry , endocrinology , sch 23390 , medicine , kainic acid , glutamate decarboxylase , pars reticulata , dopamine , glutamate receptor , receptor , biology , biochemistry , enzyme
The recently alleged neurotoxicity of the D 1 receptor agonist, SKF 38393, was investigated in rat striatum by measuring the enzymes acetylcholinesterase (AChE) and glutamate decarboxylase (GAD). First, unilateral intrastriatal microinjection of the excitotoxin kainic acid (2 μg in 1 μ1) was shown to evoke vigorous contraversive circling, followed 1 or 2 weeks later by profound decreases in striatal AChE (24 and 54%), GAD (51 and 75%), and protein (36 and 47%), as well as loss of GAD (45% at 2 weeks) in the ipsilateral substantia nigra. Similar striatal treatments with SKF 38393 (30 μg in 0.5–1 μ), the related benzazepines SKF 82526 (D 1 agonist, 30 μg in 1 μ1) and SCH 23390 (D 1 antagonist, 5 μg in 1 μ1), or the phenanthridine D 1 agonist CY 208‐243 (5 μg in 1 μ1) failed to affect the rats' behaviour or their striatal levels of AChE, GAD, and protein. Intrastriatal SKF 38393 (30 μg in 0.5 μ1) also had no influence on these enzymes in the substantia nigra. It is concluded that none of the D 1 dopaminergic compounds examined here was neurotoxic toward the many different cell groups that contain AChE and/or GAD in the striatum.