Serotonin transporter expression in rat brain regions and blood platelets: aging and glucocorticoid effects.
Hyperactivity of the hypothalamus-pituitary-adrenal axis is more common in elderly depression than in younger cohorts and glucocorticoids are known to influence serotonergic systems. The current study explores the interaction of glucocorticoids with aging on serotonin transporter expression and function. Continuous infusions of dexamethasone (26 days) reduced transporter expression in the aged brain but the ability of imipramine to inhibit synaptosomal [3H]serotonin uptake was unimpaired. These effects were unique to aged animals, as prior work with young adults found no effects of dexamethasone on transporter expression. In contrast to the effects in the brain, there were no differences in platelet transporter expression between young and old rats nor did dexamethasone treatment affect the values in the aged group: thus, the platelet may not reliably model these aspects of CNS function. The results suggest that there are basic biologic differences in the effects of glucocorticoids in aged vs. young brain that could contribute to lowered effectiveness to antidepressants in elderly depression; if transport capacity is already reduced by the effects of increased glucocorticoids, further inhibition of transport by antidepressants would have proportionally less impact on synaptic serotonin concentrations.
Slotkin
T A
TA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.
McCook
E C
EC
Ritchie
J C
JC
Carroll
B J
BJ
Seidler
F J
FJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001931:Brain Mapping; D002352:Carrier Proteins / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000493:pharmacokinetics; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000097:blood; D050486:Serotonin Plasma Membrane Transport Proteins; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D005938:Glucocorticoids; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin; D017374:Paroxetine; D003907:Dexamethasone; D007099:Imipramine