5-HT1A receptors are differentially involved in the anxiolytic- and antidepressant-like effects of 8-OH-DPAT and fluoxetine in the rat.
Fluoxetine, a selective serotonin reuptake inhibitor, shows moderate efficacy and potency in the rat forced swimming depression test and the shock-induced ultrasonic vocalization anxiety test, whereas the 5-HT(1A) receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is highly efficient and potent in both models. Whereas the 5-HT(1A) receptor antagonist WAY 100,635 abolishes the effect of 8-OH-DPAT in both models, it only attenuates the antidepressant-like effect of fluoxetine. Pretreatment with the 5-HT-depleting agent parachlorophenylalanine attenuates the antidepressant-like effect of fluoxetine, but not that of 8-OH-DPAT. This suggests that the antidepressant-like effect of fluoxetine and 8-OH-DPAT results from indirect (via increased synaptic availability of 5-HT) and direct stimulation of postsynaptic 5-HT(1A) receptors, respectively; whereas the anxiolytic-like effect of fluoxetine is not mediated by 5-HT(1A) receptors. The data support the hypothesis that the antidepressant- and anxiolytic-like effect of 8-OH-DPAT is predominantly mediated by post- and presynaptic 5-HT(1A) receptors, respectively, and that 5-HT(1A) receptors are only partially involved in the antidepressant-like effect of fluoxetine.
De Vry
J
J
CNS Research, Bayer HealthCare, Aprather Weg 18a, 42096 Wuppertal, Germany. Jean.DeVry@Grunenthal.de
Schreiber
R
R
Melon
C
C
Dalmus
M
M
Jentzsch
K R
KR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D010134:Fenclonine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013550:Swimming / Q000523:psychology; D014828:Vocalization, Animal / Q000187:drug effects
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D010134:Fenclonine; D005473:Fluoxetine; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; D017661:Receptors, Presynaptic; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide