Indorenate produces antidepressant-like actions in the rat forced swimming test via 5-HT1A receptors.
BACKGROUND
Indorenate has been proposed to possess antihypertensive, anorectic, stimulus control and anxiolytic-like actions. This compound has affinity mainly for the serotonergic(1A/1B) receptors, hence it could possess antidepressant-like activity.


OBJECTIVE
The general purpose of this study was to explore the possible antidepressant-like effects of the serotonergic compound indorenate in the forced swimming test (FST).


METHODS
In a first approach, a comparison of the actions of several doses of indorenate (2.5, 5.0, 10 mg/kg) with those of other 5-HT(1A) agonists, buspirone (5.0, 10.0 mg/kg) and 8-OH-DPAT (0.25, 0.50, 1.0 mg/kg), was performed in the FST. Secondly, in order to determine the serotonergic receptors that are participating in indorenate's action, different doses of serotonergic antagonists were administered. The compounds used were the 5-HT(1A/1B) and beta-adrenergic antagonist pindolol (2.5, 5.0 mg/kg), the 5-HT(1B)receptor antagonist GR 55562 (0.75, 1.5, 3.0 mg/kg), the 5-HT(1A) antagonist WAY 100635 (0.25, 0.5, 1.0 mg/kg) and the 5-HT(2) antagonist ketanserin (1.0, 2.0, 4.0 mg/kg).


RESULTS
Indorenate (10 mg/kg), 8-OH-DPAT (1.0 mg/kg) and buspirone (5.0 and 10.0 mg/kg) reduced immobility behaviour in the FST, considered as an antidepressant-like effect. Both doses of pindolol (2.5 and 5.0 mg/kg) and WAY 100635 (0.5 and 1.0 mg/kg) antagonised the antidepressant-like effect of indorenate. Neither 5-HT(1B) (GR55562) nor 5-HT(2)(ketanserin) antagonists produced changes in the effect of indorenate in the FST.


CONCLUSIONS
Indorenate produces antidepressant-like actions in the FST that are mediated by the stimulation of 5-HT(1A) receptors.
Martínez-Mota
Lucía
L
Subdirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, México 14370, D.F. lucia@imp.edu.mx
Estrada-Camarena
Erika
E
López-Rubalcava
Carolina
C
D008735:5-Methoxytryptamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D002065:Buspirone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010869:Pindolol / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013550:Swimming / Q000502:physiology / Q000523:psychology
D000928:Antidepressive Agents; D001549:Benzamides; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C103477:3-(3-(dimethylamino)propyl)-4-hydroxy-N-(4-(4-pyridinyl)phenyl)benzamide; D008735:5-Methoxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; C033600:indorenate; D010869:Pindolol; D002065:Buspirone