Influence of chronic administration of antidepressant drugs on mRNA for galanin, galanin receptors, and tyrosine hydroxylase in catecholaminergic and serotonergic cell-body regions in rat brain.
Activity of locus coeruleus (LC) neurons and release of the peptide galanin (GAL), which is colocalized with norepinephrine (NE) in LC neurons, has been implicated in depression and, conversely, in antidepressant action. The present study examined the influence of chronic administration (for 14days, via subcutaneously-implanted minipump) of antidepressant (AD) drugs representing three different classes (tricyclic [desipramine], selective serotonin reuptake inhibitor [SSRI] [paroxetine], and monoamine oxidase inhibitor [MAOI] [phenelzine]) on mRNA for GAL, GAL receptors (GalR1, GalR2, and GalR3), and tyrosine hydroxylase (TH), the rate-limiting enzyme for NE synthesis, in four brain regions--LC, A1/C1, dorsal raphe (DRN), and ventral tegmentum (VTA) of rats. Consistent with previous findings that chronic administration of AD drugs decreases activity of LC neurons, administration of AD drugs reduced mRNA for both GAL and TH in LC neurons. GAL and TH mRNA in LC neurons was highly correlated. AD drugs also reduced GAL and TH mRNA in A1/C1 and VTA but effects were smaller than in LC. The largest change in mRNA for GAL receptors produced by AD administration was to decrease mRNA for GalR2 receptors in the VTA region. Also, mRNA for GalR2 and GalR3 receptors was significantly (positively) correlated in all three predominantly catecholaminergic brain regions (LC, A1/C1, and VTA). Relative to these three brain regions, unique effects were seen in the DRN region, with the SSRI elevating GAL mRNA and with mRNA for GalR1 and GalR3 being highly correlated in this brain region. The findings show that chronic administration of AD drugs, which produces effective antidepressant action, results in changes in mRNA for GAL, GAL receptors, and TH in brain regions that likely participate in depression and antidepressant effects.
Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, USA.
Molly L
ML
Rovin
Katherine A
KA
Boss-Williams
Reid S
RS
Alisch
James C
JC
Ritchie
David
D
Weinshenker
Charles H K
CH
West
Jay M
JM
Weiss
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D002395:Catecholamines / Q000378:metabolism; D019004:Galanin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044088:Receptors, Galanin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D000928:Antidepressive Agents; D002395:Catecholamines; D012333:RNA, Messenger; D044088:Receptors, Galanin; D012701:Serotonin; D019004:Galanin; D014446:Tyrosine 3-Monooxygenase