Lack of β adrenoceptor desensitization in brain following the dual noradrenaline and serotonin reuptake inhibitor venlafaxine

• Published in: European neuropsychopharmacology Vol. 8; no. 3; pp. 227 - 232
• Main Authors: Nalepa, Irena, Manier, D.Hal, Gillespie, David D., Rossby, S.Paul, Schmidt, Dennis E., Sulser, Fridolin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.1998
• Subjects: Adenylyl Cyclases - drug effects; Animals; Beta adrenoceptors; Brain - metabolism; Brain Chemistry - drug effects; Cyclic AMP - metabolism; Cyclic AMP responses; Cyclohexanols - pharmacology; Male; Noradrenaline; Norepinephrine - antagonists & inhibitors; Norepinephrine - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta - drug effects; Serotonin; Serotonin - pharmacology; Serotonin Uptake Inhibitors - pharmacology; Venlafaxine; Venlafaxine Hydrochloride; Venlafaxine; Serotonin; Cyclic AMP responses; Beta adrenoceptors; Noradrenaline
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/S0924-977X(97)00078-3

Venlafaxine, a dual amine reuptake inhibitor, was utilized to delineate the role of the individual aminergic components of the `serotonin/noradrenaline link' in modifying receptor-linked second messenger cascades. Venlafaxine (20 mg/kg i.p. bid for 10 days) failed to alter in normal animals either the density of β adrenoceptors or the response of the β adrenoceptor-coupled adenylate cyclase system to noradrenaline but significantly decreased the cyclic AMP response to noradrenaline in the brain of rats with selective depletion of brain serotonin by p-chlorophenylalanine. The studies provide evidence for a cross-talk between noradrenergic and serotonergic receptor cascades at the level of mechanisms involved in the desensitization of the β adrenoceptor-coupled adenylate cyclase system.