Abstract:
: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 Bmax value of [3H]-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.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Grecksch G,Zhou D,Franke C,Schröder U,Sabel B,Becker A,Huether Gdoi
10.1038/sj.bjp.0701530subject
Has Abstractpub_date
1997-12-01 00:00:00pages
1725-31issue
8eissn
0007-1188issn
1476-5381journal_volume
122pub_type
杂志文章abstract::1 alpha-Flupenthixol (alpha-FPT; 0.2 mg/kg i.p.) when administered to rats produced catalepsy. 2 Baclofen (10 mg/kg i.p.) given 30 min after alpha-FPT had a biphasic effect on the catalepsy. Initially there was a potentiation of the effect, followed by a significant attenuation of the degree of catalepsy. 3 Possible m...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb08460.x
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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更新日期:1980-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13027
更新日期:2015-04-01 00:00:00
abstract::1. The mechanism underlying the anticataleptic properties of the atypical neuroleptic agent, clozapine, has been investigated in the rat. 2.The close structural analogues of clozapine, loxapine (0.1 mg kg(-1) s.c.) and iso-clozapine (1 and 3 mg kg(-1) s.c.) induced catalepsy in rats. In contrast, clozapine and the reg...
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journal_title:British journal of pharmacology
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更新日期:2007-07-01 00:00:00