Galanin, galanin receptor subtypes and depression-like
behaviour
E. Kuteeva, T. Hçkfelt, T. Wardi and S. O. Ögren
*
Department of Neuroscience, Karolinska Institutet, Retzius väg. 8, S-171 77 Stockholm (Sweden),
Fax : +468302875, e-mail: Sven.Ove.Ogren@ki.se
Online First 27 May 2008
Abstract. The pathophysiology of depression remains
unclear, but involves disturbances in brain monoami-
nergic transmission. Current antidepressant drugs,
which act by enhancing this type of transmission, have
limited therapeutic efficacy in a number of patients,
and not rarely serious side-effects. Increasing evi-
dence suggests that neuropeptides, including galanin,
can be of relevance in mood disorders. Galanin is co-
expressed with and modulates noradrenaline and
serotonin systems, both implicated in depression.
Pharmacological and genetic studies have suggested
a role for galanin in depression-like behaviour in
rodents, whereby the receptor subtype involved
appears to play an important role. Thus, stimulation
of GalR1 and/or GalR3 receptors results in depres-
sion-like phenotype, while activation of the GalR2
receptor attenuates depression-like behaviour. These
findings suggest that galanin receptor subtypes repre-
sent targets for development of novel antidepressant
drugs. (Part of a Multi-author Review)
Keywords. Depression-like behaviour, galanin, galanin receptor, noradrenaline, serotonin.
Introduction
Mood disorders, including the most severe forms such
as major depression and bipolar disorder (manic-
depressive illness), are among the most prevalent
mental illnesses. It is estimated that about 10–20% of
the people in the Western world suffer from depres-
sive episodes during their lifetime [1]. According to
the diagnostic criteria, depression is characterised by a
number of symptoms, including abnormal lowering of
mood (melancholia), low self-esteem and feelings of
hopelessness, blunting of brain reward systems (anhe-
donia), anxiety, irritability, disturbances of sleep,
dysfunctions in food intake, sexual dysfunctions and
cognitive disturbances [2]. The Global Burden of
Disease Study has identified major depressive disor-
der among the leading causes of disability worldwide,
and as an illness representing a growing health, social
and economical problem [3, 4].
Depression: monoamine hypotheses
The aetiology of depression is still not well charac-
terised, but involves interactions between genetic and
social predisposing factors, including exposure to
traumatic (distressing) events [5, 6]. During the past
four decades much research has focused on the
catecholamine hypothesis of depression [7]. This
hypothesis stems from the observation that mono-
amine oxidase inhibitors (MAOIs) and tricyclic anti-
depressants (TCAs), which both increase noradrena-
line (NA) transmission, have antidepressant proper-
ties.
The early catecholamine hypothesis proposed that
depressive symptoms are related to a deficiency in NA
in the brain [7]. Subsequent studies, on the other hand,
proposed that brain NA transmission is dysregulated
in depressed patients [8]. More recent hypotheses
have emphasised the maladaptive nature of catechol-
amine transmission in depression. Thus, while the
basal NA transmission is reduced, the stress-induced
NA response is actually amplified in depressed
patients [9–11].
* Corresponding author.
Cell. Mol. Life Sci. 65 (2008) 1854 – 1863
1420-682X/08/121854-10
DOI 10.1007/s00018-008-8160-9
Birkhäuser Verlag, Basel, 2008
Cellular and Molecular Life Sciences