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Influence of olfactory bulbectomy and subsequent imipramine treatment on 5‐hydroxytryptaminergic presynapses in the rat frontal cortex: behavioural correlates
Author(s) -
Grecksch Gisela,
Zhou Dan,
Franke Christian,
Schröder Ulrike,
Sabel Bernhard,
Becker Axel,
Huether Gerald
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701530
Subject(s) - imipramine , endocrinology , medicine , antidepressant , clonazepam , frontal cortex , cortex (anatomy) , tryptophan hydroxylase , psychology , chemistry , serotonin , neuroscience , serotonergic , hippocampus , receptor , psychiatry , alternative medicine , pathology
1 Alterations of 5‐hydroxytryptaminergic mechanisms are thought to play a special role in the pathogenesis of depression and antidepressant treatments are assumed to restore these changes. 2 We have used one of the most reliable models of depression, the olfactory bulbectomized rat to study the long term consequences of this manipulation and of subchronic imipramine treatment on two parameters of 5‐hydroxytryptaminergic presynapses, 5‐hydroxytryptamine (5‐HT) transporter density and tryptophan hydroxylase apoenzyme concentration, in the frontal cortex as well as on active avoidance learning several weeks after bulbectomy. 3 The B max value of [ 3 H]‐paroxetine binding and the concentration of the 5‐HT synthesizing enzyme were both significantly elevated in the frontal cortex of bulbectomized rats compared to sham‐operated controls. 4 Imipramine treatment, either by daily injections or by subcutaneous implantation of slow release imipramine‐containing polymers reduced the elevated tryptophan hydroxylase apoenzyme levels in the frontal cortex of bulbectomized, but not of sham‐operated control rats and restored the deficient learning performance of bulbectomized rats. 5 Both effects were more pronounced after continuous drug administration by imipramine‐releasing polymers compared to daily i.p. injections. 6 These findings indicate that bulbectomy leads to a compensatory 5‐hydroxytryptaminergic hyperinnervation of the frontal cortex. Chronic antidepressant treatment seems to attenuate the increased output of the 5‐hydroxytryptaminergic projections in the frontal cortex through the destabilization of the rate limiting enzyme of 5‐HT synthesis of the 5‐hydroxytryptaminergic nerve endings in this brain region.