5-Hydroxytryptamine1A receptor agonists in animal models of depression and anxiety.
The effects of different doses of buspirone, 3-dipropyl-amino-5-hydrochromar (NDO 008) and 8-hydroxydipropyl-aminotetralin (8-OH-DPAT) (administered intraperitoneally) were studied in tests of anxiolytic and antidepressant action in rats. These tests included the elavated plus maze test, the forced swim test, stress-induced suppression of open-field behavior, and the differential-reinforcement-of-low-rates-of-behaviour-72 sec (DRL 72 s) test. Buspirone (0.125 mg/kg) and NDO 008 (1.0 to 2.0 mg/kg) produced anxiolytic activity in the elevated plus maze, whereas 8-OH-DPAT did not in the doses employed. All three compounds increased activity in the forced swim test, although buspirone did so at a lower dose than NDO 008 and 8-OH-DPAT. In the stress-induced suppression test of open field activity all three compounds induced an antidepressant-like effect at different doses dependent on whether footshock (stressor) was presented 24 hr before or just prior to the open-field test. All three compounds even caused some reduction of activity in the non-shocked rats. 8-OH-DPAT (1.0 mg/kg) produced a significant and reliable increase in the Reinforcement/Response rate quotient in the DRL 72s test. These diverse results may provide an indication of potential clinical efficacy of the 5-HT1A agonists in the treatment of anxiety and depression.
Kostowski
W
W
Department of Pharmacology and Physiology of the Nervous System, Psychoneurological Institute, Warszawa, Poland.
Dyr
W
W
Krzascik
P
P
Järbe
T
T
Archer
T
T
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D002065:Buspirone / Q000008:administration & dosage / Q000627:therapeutic use*; D002839:Chromans / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000627:therapeutic use*
D002839:Chromans; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C071048:3-propylamino-5-hydroxychroman; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone