sb-271046 and Depressive-Disorder

Using in vivo microdialysis in the freely moving rat we have examined the effects of 5-HT(6) receptor antagonism on the neurochemical outcome of antidepressant treatment. Acute administration of both desipramine (10 mg/kg s.c.) and venlafaxine (10 mg/kg s.c.) produced a 2 fold increase in extracellular noradrenaline (NA) but no change in frontal cortex dopamine (DaA), 5-HT or glutamate. Fluoxetine (20 mg/kg s.c.) produced no change in extracellular levels of any of the neurotransmitters examined. SB-271046 produced a 3 fold increase in extracellular glutamate. Combination treatment of SB-271046 with each antidepressant produced no change in the antidepressant-induced changes in NA, DA or 5-HT. In contrast, both fluoxetine and venlafaxine attenuated the SB-271046-induced increase in extracellular glutamate, suggesting that 5-HT and possibly NA may be having an inhibitory action on the excitatory pathways enhanced by 5-HT(6) receptor blockade. Furthermore, these data indicate that the neurochemical effects induced by NA and/or 5-HT reuptake inhibitors are not enhanced by 5-HT(6) receptor blockade indicating that 5-HT(6) receptor antagonists are unlikely to augment the therapeutic efficacy of these types of antidepressants.

Topics: Adrenergic Uptake Inhibitors; Animals; Antidepressive Agents; Cyclohexanols; Depressive Disorder; Desipramine; Drug Synergism; Extracellular Space; Fluoxetine; Glutamic Acid; Male; Microdialysis; Neurons; Norepinephrine; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Antagonists; Sulfonamides; Synaptic Transmission; Thiophenes; Venlafaxine Hydrochloride