ISSN:
1432-1912
Keywords:
Key words Imidazoline receptors
;
α2-adrenoceptors
;
Dopa/noradrenaline synthesis
;
Dopa/dopamine synthesis
;
5-HTP/serotonin synthesis
;
Rat brain
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract This study was designed to assess the effects of imidazoline drugs on putative presynaptic imidazoline receptors modulating brain monoamine synthesis in vivo. The accumulation of 3,4-dihydroxyphenylalanine (dopa) and 5-hydroxytryptophan (5-HTP) after decarboxylase inhibition was used as a measure of the rate of tyrosine and tryptophan hydroxylation in various brain regions of naive rats and after irreversible α2-adrenoceptor inactivation with EEDQ (1.6 mg/kg, i.p., 6 h). Clonidine (1–3 mg/kg), moxonidine (1–10 mg/kg) and rilmenidine (10 mg/kg) (mixed I1/α2 agonists) decreased dopa and 5-HTP synthesis in the cerebral cortex (14%–81%), hippocampus (27%–84%) and/or striatum (29%–56%), but these inhibitory effects were abolished in N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-treated rats. Similarly, the stimulatory effect of efaroxan (mixed I1/α2 antagonist; 10 mg/kg) on dopa synthesis in the cortex (77%) and hippocampus (57%) was abolished by EEDQ. The selective I1-ligand 2-endo-amino-3-exo-isopropylbicyclo-heptane (AGN-192403; 5–10 mg/kg) did not modify dopa or 5-HTP synthesis in any brain region in naive or EEDQ-treated rats. Idazoxan (mixed I2/α2 antagonist; 20 mg/kg) increased dopa synthesis in the cortex (111%) and hippocampus (87%), but the stimulatory effects were abolished by EEDQ. Moreover, idazoxan and efaroxan decreased 5-HTP synthesis in the cortex (12%–34%) and hippocampus (30%–34%) in a manner sensitive to blockade by the 5-HT1A receptor antagonist WAY 100135. The selective I2-ligands 2-(2-benzofuranyl)-2-imidazoline (2-BFI; 20 mg/kg) and 2-styryl-2-imidazoline (LSL 61122; 10 mg/kg) did not alter the synthesis of dopa or 5-HTP in the cortex or hippocampus. In striatum, 2-BFI (1–20 mg/kg) dose-dependently decreased dopa synthesis (ED50: 5.9 mg/kg), reduced dopamine levels (6%–36%) and increased those of its metabolites DOPAC (15%–95%) and HVA (24%–74%). The inhibitory effect of 2-BFI on dopa/dopamine synthesis in striatum remained unchanged after alkylation of imidazoline receptors with isothiocyanatobenzyl imidazoline (IBI; 60 mg/kg, 6 h) or blockade of these receptors with 2-(2-ethyl 2,3-dihydro-2-benzofuranyl)-2-imidazole (KU-14R; 7–20 mg/kg). Therefore, most imidazoline drugs modulated the synthesis of brain monoamines through interaction with α2-adrenoceptors or 5-HT1A receptors. The results do not provide functional evidence for the existence of presynaptic imidazoline receptors regulating the synthesis of monoamines in the rat brain.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002109900032
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