title: Varenicline has antidepressant-like activity in the forced swim test and augments sertraline's effect.
abstract: Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist developed as a smoking cessation aid, showed antidepressant-like activity in the forced swim test in two mouse strains. In addition, a low varenicline dose significantly enhanced the effects of moderately active doses of the selective serotonin reuptake inhibitor sertraline. These findings are consistent with the notion that reducing alpha4beta2 nicotinic acetylcholine receptor activity either by antagonists or by partial agonists that can partially activate or desensitize acetylcholine receptors is associated with antidepressant-like properties. These data suggest that varenicline may have antidepressant potential and can, when combined, augment antidepressant responses of selective serotonin reuptake inhibitors.
authors.affiliation: Department Neuroscience, Pfizer Global Research and Development, Groton, CT 06340, USA. hans.rollema@pfizer.com
authors.forename: Hans
authors.initials: H
authors.lastname: Rollema
authors.forename: Victor
authors.initials: V
authors.lastname: Guanowsky
authors.forename: Yann S
authors.initials: YS
authors.lastname: Mineur
authors.forename: Alka
authors.initials: A
authors.lastname: Shrikhande
authors.forename: Jotham W
authors.initials: JW
authors.lastname: Coe
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Seymour
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D011978:Receptors, Nicotinic; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D020280:Sertraline / Q000494:pharmacology; D013550:Swimming; D000068580:Varenicline
chemical_list: D000928:Antidepressive Agents; D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D011978:Receptors, Nicotinic; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D000068580:Varenicline; C403531:nicotinic receptor alpha4beta2