Antidepressants and Receptor Function

Ciba Foundation Symposium 123 Antidepressants and Receptor FunctionChairman: Dennis Murphy, 1986 Depression is a common and often debilitating affective disorder. Attempts to develop effective antidepressants have a long history, but many questions remain about the mechanisms of action of such treatments and about the aetiology and pathophysiology of depression itself. Early observations centred attention on central monoamine systems, and animal studies suggested that changes in beta-adrenoceptor responsiveness were a common effect of antidepressant therapies. More recent research has encompassed many different central and peripheral receptors, time-dependent adaptational events at synapses, and the functional significance of changes in neurotransmitter systems in both humans and experimental animals. Such pharmacological studies aimed ultimately at elucidating the neurochemical basis of depression and of promoting new therapeutic approaches, provide the focus of this symposium volume. Many different methods of investigating the links between monoamine systems, depression and antidepressant treatments are described. Recent studies of receptors and of monoamine uptake sites in the brain and the periphery (e.g. in platelets and fibroblasts) are reviewed, with emphasis on alpha and beta adrenoceptors, [3H]imipramine-binding sites and serotonin receptors. The results of monitoring amine metabolites in cerebrospinal fluid and of measuring neuroendocrine, physiological and behavioural responses to pharmacological challenge are presented, providing information on monoaminergic function in depressed patients and experimental animals before, during and after treatment with antidepressant drugs or electroconvulsive shock. Genetic influences on receptor density are also discussed, as is the relevance to human depressive illness of animal models, including stress-induced behavioural depression in rats and responses to social stressors in rhesus monkeys. This book should be of interest to neuropharmacologists, psychopharmacologists, clinical pharmacologists, behavioural scientists, psychiatrists and neuroscientists.

Ciba Foundation Symposium 123 Antidepressants and Receptor FunctionChairman: Dennis Murphy, 1986Depression is a common and often debilitating affective disorder. Attempts to develop effective antidepressants have a long history, but many questions remain about the mechanisms of action of such treatments and about the aetiology and pathophysiology of depression itself. Early observations centred attention on central monoamine systems, and animal studies suggested that changes in beta-adrenoceptor responsiveness were a common effect of antidepressant therapies. More recent research has encompassed many different central and peripheral receptors, time-dependent adaptational events at synapses, and the functional significance of changes in neurotransmitter systems in both humans and experimental animals. Such pharmacological studies aimed ultimately at elucidating the neurochemical basis of depression and of promoting new therapeutic approaches, provide the focus of this symposium volume. Many different methods of investigating the links between monoamine systems, depression and antidepressant treatments are described. Recent studies of receptors and of monoamine uptake sites in the brain and the periphery (e.g. in platelets and fibroblasts) are reviewed, with emphasis on alpha and beta adrenoceptors, [³H]imipramine-binding sites and serotonin receptors. The results of monitoring amine metabolites in cerebrospinal fluid and of measuring neuroendocrine, physiological and behavioural responses to pharmacological challenge are presented, providing information on monoaminergic function in depressed patients and experimental animals before, during and after treatment with antidepressant drugs or electroconvulsive shock. Genetic influences on receptor density are also discussed, as is the relevance to human depressive illness of animal models, including stress-induced behavioural depression in rats and responses to social stressors in rhesus monkeys.This book should be of interest to neuropharmacologists, psychopharmacologists, clinical pharmacologists, behavioural scientists, psychiatrists and neuroscientists.

Symposium on Depression, antidepressants and receptor sensitivityheld at the Ciba Foundation, London, 19-21 November 1985Editors: Ruth Porter, Gregory Bock (Organizer) and SarahClarkD. Murphy IntroductionS.Z. Langer, A.M. Galzin, C.R. Lee and H. SchoemakerAntidepressant-binding sites in brain and plateletsDiscussionW.H. Berrettini, J. Bardakjian, A.L. Barnett Jr, J.I. NurnbergerJr and E.S. Gershon beta-Adrenoceptor function in human adultskin fibroblasts: a study of manic-depressive illnessDiscussionP. Propping, W. Friedl, J. Hebebrand and K-U. Lentes Geneticstudies at the receptor level: investigations in human twins andexperimental animalsDiscussionM. Åsberg and A. Wägner Biochemical effects ofantidepressant treatment--studies of monoamine metabolites incerebrospinal fluid and platelet [³H]imipraminebindingDiscussionR.W. Horton, C.L.E. Katona, A.E. Theodorou, A.S. Hale, S.L.Davies, C. Tunnicliffe, Y. Yamaguchi, E.S. Paykel and J.S. KellyPlatelet radioligand binding and neuroendocrine challenge tests indepressionDiscussionD.L. Murphy, C.S. Aulakh and N. A. Garrick How antidepressantswork: cautionary conclusions based on clinical and laboratorystudies of the longer-term consequences of monoamineoxidase-inhibiting antidepressantsDiscussionS.A. Checkley, T.H. Corn, I.B. Glass, C. Thompson, C. Franey andJ. Arendt Neuroendocrine and other studies of the mechanism ofantidepressant action of desipramineDiscussionL.J. Siever, E.F. Coccaro, E. Benjamin, K. Rubinstein and K.L.Davis Adrenergic and serotonergic receptor responsiveness indepressionDiscussionGeneral discussion IA. Frazer, G. Ordway, J. O'Donnell, P. Vos and B. WolfeEffect of repeated administration of clenbuterol on the regulationof beta-adrenoceptors in the central nervous system of theratDiscussionJ.M. Weiss and P.G. Simson Depression in an animal model: focuson the locus ceruleusDiscussionG.W. Kraemer Causes of changes in brain noradrenaline systemsand later effects on responses to social stressors in rhesusmonkeys: the cascade hypothesisDiscussionJ. Vetulani, L. Antkiewicz-Michaluk, A. Rokosz-Pelc and J.Michaluk Effects of chronically administered antidepressants andelectroconvulsive treatment on cerebral neurotransmitter receptorsin rodents with 'model depression'DiscussionA.R. Green, D.J. Heal and G.M. Goodwin The effects ofelectroconvulsive therapy and antidepressant drugs on monoaminereceptors in rodent brain--similarities and differencesDiscussionGeneral discussion IIClosing remarksIndex of contributorsSubject index