Desmethylimipramine pretreatment prevents 6-hydroxydopamine induced somatostatin receptor reduction in the rat hippocampus.
Several studies have shown anatomical and functional interconnections between catecholaminergic and somatostatinergic systems. To assess whether somatostatin (SS) may act presynaptically on catecholamine neurons, SS receptors were measured using radioligand test-tube binding assays on synaptosomes from hippocampus and frontoparietal cortex--areas that are innervated by catecholaminergic neurons with different densities and that have a high number of SS receptors--from control and 6-hydroxydopamine (6-OHDA)-treated rats. Intracerebroventricular (i.c.v.) injection of the catecholamine neurotoxin 6-OHDA (0.78 mg free base/kg of body weight in saline with 0.1% ascorbic acid) lowered hippocampal and frontoparietal cortical noradrenaline (NA) and dopamine (DA) levels at 1 week following the injection. Pretreatment of rats with desmethylimipramine (DMI) (40 mg/kg, intraperitoneal) prevented the drop in NA levels, but was not effective in attenuating DA depletion in the two brain areas studied. Treatment with 6-OHDA lowered the number of 125I-Tyr11-SS receptors in the hippocampus (130 +/- 19 vs. 266 +/- 16 fmol/mg protein, P < 0.001), whereas in the frontoparietal cortex a non significant 20% reduction in receptor number was found. The dissociation constants of 125I-Tyr11-SS binding to synaptosomes from frontoparietal cortex (0.65 +/- 0.06 vs. 0.60 +/- 0.04, P not significant) and hippocampus (0.44 +/- 0.04 vs. 0.63 +/- 0.14, P not significant) were similar in control and treated groups. Pretreatment with DMI reversed up to 80% of the effect of 6-OHDA on hippocampus SS receptors. DMI alone had no observable effect on the number and affinity of SS receptors. The 6-OHDA and the DMI treatment did not affect SLI levels in the brain areas studied. These results suggest that a portion of the hippocampal SS receptors may be localized presynaptically on the noradrenergic and dopaminergic nerve terminals.
López-Sañudo
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S
Department of Biochemistry and Molecular Biology, Medical School, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Arilla
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D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000187:drug effects* / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017481:Receptors, Somatostatin; D016627:Oxidopamine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine