PMID: 6974869Jul 1, 1981Paper

Postsynaptic action by four antidepressive drugs in an animal model of depression

Pharmacology, Biochemistry, and Behavior
H NagayamaM H Aprison

Abstract

To further test the new hypersensitive postsynaptic serotonin (5-HT) receptor theory of depression bases on or animal model, it was necessary to demonstrate that some of the currently used antidepressive drugs can block D,L-5-hydroxytryptophan (5-HTP) induced depression acting through postsynaptic rather than presynaptic mechanisms. Rats working for milk reinforcement and exhibiting behavioral depression following administration of 5-HTP (IP) were pretreated (1 hour before the 5-HTP injection) with fluoxetine (5 mg/kg IP) or methysergide (5 mg/kg IP) to establish a behavioral basis for distinguishing between pre- and postsynaptic events, respectively. Fluoxetine, a known specific uptake blocker of 5-HT, potentiated the depressive effect of 12.5 mg/kg 5-HTP by 200%. Methysergide, a postsynaptic blocker of 5-HT, almost completely (93%) abolished the depressive effect of 50 mg/kg 5-HTP. Since acute pretreatment with comparable clinical doses of the antidepressive drugs, mianserin, amitriptyline, imipramine, or iprindole, resulted in blockade of the 5-HTP induced depression by 70, 50, 40, and 20% respectively, these drugs can act as antagonists of 5-HT at the postsynaptic serotonin receptor. When these results are viewed in terms o...Continue Reading

References

Sep 15, 1978·Psychopharmacology·J MajA Rawłów
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Oct 1, 1980·Pharmacology, Biochemistry, and Behavior·H NagayamaM H Aprison
Apr 15, 1960·Experientia·M H APRISON, C B FERSTER

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Citations

Jan 1, 1984·Psychopharmacology·P Willner
Jul 1, 1985·Biological Psychiatry·J A Jesberger, J S Richardson
Jul 1, 1986·Biological Psychiatry·J D Leander
Dec 15, 1984·European Journal of Pharmacology·D LuttingerM Perrone
Jan 1, 1986·Physiology & Behavior·F BorsiniA Meli
Nov 1, 1982·Pharmacology, Biochemistry, and Behavior·L BrownE P Riley
Jun 1, 1985·Pharmacology, Biochemistry, and Behavior·E L EchandíaM R Fóscolo
Aug 1, 1986·Pharmacology, Biochemistry, and Behavior·E EdwardsF A Henn
Feb 1, 1987·Pharmacology, Biochemistry, and Behavior·K L BruggeM H Aprison
Jun 1, 1989·Pharmacology, Biochemistry, and Behavior·A R MayedaM H Aprison
Jan 1, 1991·Pharmacology, Biochemistry, and Behavior·W K ParkM H Aprison
Nov 1, 1995·Pharmacology, Biochemistry, and Behavior·E A EnglemanJ N Hingtgen
Jan 1, 1990·Pharmacology & Therapeutics·P Willner
Jan 1, 1991·Progress in Neuro-psychopharmacology & Biological Psychiatry·H NagayamaJ Akiyoshi
Jan 1, 1994·Progress in Neuro-psychopharmacology & Biological Psychiatry·J AkiyoshiH Nagayama
Aug 1, 1996·Progress in Neuro-psychopharmacology & Biological Psychiatry·F LechinM Benaim
Jan 31, 2004·Progress in Neuro-psychopharmacology & Biological Psychiatry·Rodrigo Machado-VieiraJair C Soares
Jan 1, 1984·Journal of Receptor Research·M StockertE De Robertis
Jan 1, 1988·Acta Psychiatrica Scandinavica·A KishimotoN Kunimoto
Feb 1, 1988·The International Journal of Neuroscience·J A Jesberger, J S Richardson

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