A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health

A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health

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J Psychiatry Neurosci 2012;37(1):7-16

Jean-Martin Beaulieu, PhD

Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, Centre de recherche Université Laval Robert-Giffard (CRULRG), Québec, Que.

Abstract

Mental illnesses, such as bipolar disorder, attention-deficit/hyperactivity disorder, depression and schizophrenia are a major public health concern worldwide. Several pharmacologic agents acting on monoamine neurotransmission are used for the management of these disorders. However, there is still little understanding of the ultimate molecular mechanisms responsible for the therapeutic effects of these drugs or their relations with disease etiology. Here I provide an overview of recent advances on the involvement of the signalling molecules Akt and glycogen synthase kinase-3 (GSK3) in the regulation of behaviour by the monoamine neurotransmitters dopamine (DA) and serotonin (5-HT). I examine the possible participation of these signalling molecules to the effects of antidepressants, lithium and antipsychotics, as well as their possible contribution to mental disorders. Regulation of Akt and GSK3 may constitute an important signalling hub in the subcellular integration of 5-HT and DA neurotransmission. It may also provide a link between the action of these neurotransmitters and gene products, like disrupted in schizophrenia 1 (DISC1) and neuregulin (NRG), that are associated with increased risk for mental disorders. However, changes in Akt and GSK3 signalling are not restricted to a single disorder, and their contribution to specific behavioural symptoms or therapeutic effects may be modulated by broader changes in biologic contexts or signalling landscapes. Understanding these interactions may provide a better understanding of mental illnesses, leading to better efficacy of new therapeutic approaches.


Submitted Jan. 31, 20011; Revised Apr. 5, 2011; Accepted Apr. 7, 2011.

Acknowledgments: This work was supported by the Canadian Institutes of Health Research (CIHR; grant NSA 93798) and a Natural Sciences and Engineering Research Council of Canada discovery grant. J.-M.Beaulieu holds a Canada Research Chair in Molecular Psychiatry and is a National Alliance for Research on Schizophrenia and Depression (NARSAD) Vital Projects Fund, Inc. Investigator.

Competing interests: J.-M. Beaulieu declares grants to his institution from the Canadian Institutes of Health Research, the NARSAD and the Natural Sciences and Engineering Research Council of Canada.

DOI: 10.1503/jpn.110011

Correspondence to: Dr. J.-M. Beaulieu, CRULRG, 2601 Chemin de la Canardière, Suite F-6500, Beauport QC G1J 2G3; martin.beaulieu@crulrg.ulaval.ca