title: Effects of 5-HT(6) receptor blockade on the neurochemical outcome of antidepressant treatment in the frontal cortex of the rat.
abstract: 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.
authors.affiliation: Neuroscience Research, Wyeth-Ayerst, Princeton, NJ, USA. Lee_A-Dawson@gsk.com
authors.forename: L A
authors.initials: LA
authors.lastname: Dawson
authors.forename: P
authors.initials: P
authors.lastname: Li
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D003891:Desipramine / Q000494:pharmacology; D004357:Drug Synergism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013876:Thiophenes / Q000494:pharmacology; D000069470:Venlafaxine Hydrochloride
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D003511:Cyclohexanols; D003891:Desipramine; D005473:Fluoxetine; D018698:Glutamic Acid; D009638:Norepinephrine; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; D000069470:Venlafaxine Hydrochloride; C097216:serotonin 6 receptor; C117443:SB 271046