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Acute administration of SCH23390 increases D 1 receptors on nonpyramidal neurons in rat mPFC
Author(s) -
Davidoff Stephanie A.,
Chu Hung Ming,
Benes Francine M.
Publication year - 2000
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(20000301)35:3<173::aid-syn2>3.0.co;2-u
Subject(s) - neuropil , clozapine , receptor , chemistry , antagonist , endocrinology , medicine , receptor antagonist , dopamine , downregulation and upregulation , prefrontal cortex , neuroscience , pharmacology , biology , psychology , schizophrenia (object oriented programming) , central nervous system , biochemistry , psychiatry , gene , cognition
Atypical antipsychotic drugs (APDs) such as clozapine and olanzapine antagonize both D 1 and D 2 receptors; however, little is known regarding their pharmacologic effect on specific neuronal elements within the local circuitry of corticolimbic regions, such as medial prefrontal cortex (mPFC). To characterize the effect of short‐term antagonism of the D 1 receptor a high‐resolution autoradiographic technique was used to assess the density (B max ) and affinity (K d ) of this receptor on pyramidal cells (i.e., large neurons (LNs, ≥100 μm 2 )), nonpyramidal cells (i.e., small neurons (SNs, <100 μm 2 )) and in the surrounding neuropil (NPL) of layer VI in rat mPFC. Either normal saline or the selective D 1 antagonist SCH23390 (1.0 mg/kg/day) were administered for 48 h via Alzet osmotic pumps. Frozen sections were incubated in [ 3 H]SCH23390 (1–8 nM) in the presence or absence of the competitive inhibitor SKF38393 (10 μM). A microscopic adaptation to Scatchard analysis revealed a significant increase (82%) in B max for neuronal cell bodies ( P < 0.05), but not for neuropil of drug‐treated animals. Further analysis indicated that the increase in B max was present on SNs (94%, P < 0.05), but not LNs in SCH23390‐treated rats. In contrast, K d values for LNs, SNs, and NPL were not significantly altered by drug treatment. Since the vast majority of SNs are nonpyramidal in nature, short‐term administration of a selective D 1 antagonist seems to be associated with a preferential upregulation of this receptor on interneurons. Overall, these results are consistent with the hypothesis that the mechanism of action of atypical antipsychotic medications involves changes in D 1 receptor activity associated with local circuit neurons in rat mPFC. Synapse 35:173–181, 2000. © 2000 Wiley‐Liss, Inc.