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Pharmacol Biochem Behav. 2005 Nov;82(3):495-505. Epub 2005 Nov 28.

Differences between A 68930 and SKF 82958 could suggest synergistic roles of D1 and D5 receptors.

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1
Department of Physiology and Pharmacology, Section of Molecular Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden. Ricard.Nergardh@fyfa.ki.se

Abstract

The isochroman A 68930 and the benzazepine SKF 82958 are two full dopamine D1 receptor agonists. Responses to these compounds are different in several important aspects. When given to rats in a novel environment, A 68930 caused a dose-dependent (0.019-4.9 mg/kg) suppression of locomotion. SKF 82958 had no such effect at any dose studied (0.051-3.3 mg/kg). In animals habituated to the environment, A 68930 had no effect but SKF 82958 increased locomotor activity. Both A 68930 and SKF 82958 caused a decrease in core temperature at early time points. Both agonists increased c-fos and NGFI-A expression in caudate putamen but only SKF 82958 did so in the accumbens nucleus (at 1.6 mg/kg). Quantitative receptor autoradiography showed that A 68930 is 9-13 times more potent than SKF 82958 at displacing the selective dopamine D1 antagonist [3H]SCH 23390. This difference agrees with the difference observed when the agonists were used to stimulate cAMP formation in cells transfected with the D1 receptor. In contrast, SKF 82958 was 5 times more potent than A 68930 in cells transfected with the D5 receptor. We suggest that the balance between signaling via dopamine D1 and D5 receptors determines the functional effects of agonists at D1/D5 receptors.

PMID:
16318870
DOI:
10.1016/j.pbb.2005.09.017
[Indexed for MEDLINE]
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