WAY 100,635 enhances both the 'antidepressant' actions of duloxetine and its influence on dialysate levels of serotonin in frontal cortex.
The mixed serotonin and noradrenaline reuptake inhibitor, duloxetine, (5.0 mg/kg, s.c.), increased levels of serotonin (220%), dopamine (180%) and noradrenaline (470%) in individual dialysates of frontal cortex of freely moving rats. Its influence on serotonin, but not dopamine or noradrenaline, levels was enhanced by the 5-HT1A receptor antagonist, WAY 100,635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide 3HCl) (0.16 mg kg(-1), s.c). In the forced swimming test, although duloxetine was inactive alone, it dose dependently reduced immobility in the presence of WAY 100,635. Thus, blockade of 5-HT1A (auto)receptors selectively facilitates the influence of duloxetine on serotonin levels in the frontal cortex in rats and, in the forced swimming model, enhances its 'antidepressant' properties in parallel.
Millan
M J
MJ
I.D.R.S., 125, Croissy-sur-Seine, France.
Brocco
M
M
Veiga
S
S
Cistarelli
L
L
Melon
C
C
Gobert
A
A
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D000068736:Duloxetine Hydrochloride; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D000928:Antidepressive Agents; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D013876:Thiophenes; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D000068736:Duloxetine Hydrochloride