The effect of tianeptine and sertraline in three animal models of depression.
The activity of tianeptine (2.5 and 5.0 mg/kg twice daily, i.p.) and of sertraline (5.0 mg/kg, twice daily, i.p.) were assessed in three animal models of depression. In the Behavioural Despair Test, acute treatment with sertraline or tianeptine (5.0 mg/kg) significantly reduced the immobility time. In the olfactory bulbectomized (OB) rat model, chronic treatment with tianeptine (2.5 and 5.0 mg/kg) or sertraline (5.0 mg/kg) antagonized the lesion-induced hyperactivity in the "open field" apparatus. The hypothermic response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.15 mg/kg, s.c.) was significantly attenuated after chronic setraline treatment, whereas tianeptine was inactive at the 2 doses tested. Neither drug affected the hypersection of corticosterone that occurs at the light:dark interface. A reduction in the serotonin metabolite 5-HIAA was found in the hypothalamus of sertraline-treated sham rats. It can be concluded that although the neurochemical properties of sertraline and tianeptine differ, they demonstrate similar antidepressant-like activities in the Behavioural Despair and OB rat models. The lack of effect of tianeptine on the 8-OH-DPAT-induced hypothermic effect indicates that it does not induce 5-HT1A subsensitivity, contrary to most antidepressants.
Kelly
J P
JP
Department of Pharmacology, University College, Galway, Ireland.
Leonard
B E
BE
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D009830:Olfactory Bulb / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020280:Sertraline; D013841:Thiazepines / Q000627:therapeutic use*
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D007211:Indoles; D018377:Neurotransmitter Agents; D013841:Thiazepines; C050504:tianeptine; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D015057:1-Naphthylamine; D020280:Sertraline; D003345:Corticosterone