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In Vivo Partial Inactivation of Dopamine D 1 Receptors Induces Hypersensitivity of Cortical Dopamine‐Sensitive Adenylate Cyclase: Permissive Role of α 1 ‐Adrenergic Receptors
Author(s) -
Trovero Fabrice,
Hervé Denis,
Blanc Gérard,
Glowinski Jacques,
Tassin JeanPol
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.tb08908.x
Subject(s) - prazosin , adenylate kinase , chemistry , cyclase , sch 23390 , medicine , endocrinology , receptor , dopamine , dopamine receptor , antagonist , biology , biochemistry
As shown by autoradiography, peripheral injections of N ‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline (EEDQ) induced a dose‐dependent decrease of [ 3 H]SCH 23390 and [ 3 H]prazosin high‐affinity binding sites in the rat prefrontal cortex. EEDQ showed similar efficacy in inactivating cortical and striatal dopamine (DA) D 1 receptors, whereas prazosin‐sensitive α 1 ‐adrenergic receptors were more sensitive to the action of the alkylating agent, as for all doses of EEDQ tested (from 0.8 to 3 mg/kg, i.p.), the decrease in cortical [ 3 H]SCH 23390 binding was less pronounced than that of [ 3 H]prazosin. The effects of EEDQ on [ 3 H]SCH 23390 binding and DA‐sensitive adenylate cyclase activity were then simultaneously compared in individual rats. In the striatum, whatever the dose of EEDQ used, the decrease of DA‐sensitive adenylate cyclase activity was always lower than that of D 1 binding sites, suggesting the occurrence of a large proportion of spare D 1 receptors. In the prefrontal cortex, a significant increase in DA‐sensitive adenylate cyclase activity was observed in rats treated with a low dose of EEDQ (0.8 mg/kg), this effect being associated with a slight reduction in [ 3 H]SCH 23390 binding sites (‐20%). Parallel decreases in the enzyme activity and D 1 binding sites were observed with higher doses. The EEDQ‐induced supersensitivity of DA‐sensitive adenylate cyclase did not occur in rats in which the decrease in [ 3 H]prazosin binding sites was higher than 35%. Demonstrating further a role of noradrenergic transmission of the α 1 type in the regulation of the cortical D 1 receptor sensitivity, the blockade of α 1 ‐adrenergic receptors by prazosin prevented the appearance of the EEDQ‐induced supersensitivity of DA‐sensitive adenylate cyclase in groups of rats exhibiting similar decreases in the density of D 1 binding sites (‐20%). The DA‐sensitive adenylate cyclase activity was significantly lower in cortices of animals pretreated with prazosin than in those not treated with the α 1 antagonist. These results are discussed in relation to previous studies indicating that prazosin pretreatment also abolishes the locomotor hyperactivity induced by bilateral electrolytic lesions of the ventral teg‐mental area.