Abstract
In the rat dorsomedial hypothalamus (DMH), serotonin (5-HT) concentrations are altered rapidly in response to acute stressors. The mechanism for rapid changes in 5-HT concentrations in the DMH is not clear. We hypothesize that the mechanism involves corticosteroid-induced alterations in the uptake of 5-HT from extracellular fluid through the action of corticosterone-sensitive organic cation transporters (OCTs). To determine if OCTs affect the clearance of 5-HT from the extracellular fluid compartment within the medial hypothalamus (MH), the OCT blocker, decynium 22 (0, 10, 30, or 100 μM), was perfused into the MH via a microdialysis probe, and dialysate 5-HT concentrations were measured at 20 min intervals. In addition, home cage behavior was measured both before and after drug administration. Inhibition of OCTs in the MH resulted in a reversible dose-dependent increase in extracellular 5-HT concentration. Increases in extracellular 5-HT concentrations were associated with increases in grooming behavior in rats treated with the highest concentration of decynium 22. No other behavioral responses were observed following administration of any concentration of decynium 22. These findings are consistent with the hypothesis that OCTs in the MH play an important role in the regulation of serotonergic neurotransmission and specific behavioral responses. Because the MH plays an important role in the neuroendocrine, autonomic, and behavioral responses to stress-related stimuli, these data lead to new questions regarding the role of interactions between corticosterone and corticosterone-sensitive OCTs in stress-induced 5-HT accumulation within the MH as well as the physiological and behavioral consequences of these interactions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 69-76 |
| Number of pages | 8 |
| Journal | Brain Research |
| Volume | 1063 |
| Issue number | 1 |
| DOIs | |
| State | Published - Nov 23 2005 |
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Keywords
- Corticosterone
- Dorsomedial hypothalamus
- HPA axis
- Organic cation transporter
- Serotonin
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Local inhibition of organic cation transporters increases extracellular serotonin in the medial hypothalamus. / Feng, Na; Mo, Bing; Johnson, Philip L.; Orchinik, Miles; Lowry, Christopher A.; Renner, Kenneth J.
In: Brain Research, Vol. 1063, No. 1, 23.11.2005, p. 69-76.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Local inhibition of organic cation transporters increases extracellular serotonin in the medial hypothalamus
AU - Feng, Na
AU - Mo, Bing
AU - Johnson, Philip L.
AU - Orchinik, Miles
AU - Lowry, Christopher A.
AU - Renner, Kenneth J.
PY - 2005/11/23
Y1 - 2005/11/23
N2 - In the rat dorsomedial hypothalamus (DMH), serotonin (5-HT) concentrations are altered rapidly in response to acute stressors. The mechanism for rapid changes in 5-HT concentrations in the DMH is not clear. We hypothesize that the mechanism involves corticosteroid-induced alterations in the uptake of 5-HT from extracellular fluid through the action of corticosterone-sensitive organic cation transporters (OCTs). To determine if OCTs affect the clearance of 5-HT from the extracellular fluid compartment within the medial hypothalamus (MH), the OCT blocker, decynium 22 (0, 10, 30, or 100 μM), was perfused into the MH via a microdialysis probe, and dialysate 5-HT concentrations were measured at 20 min intervals. In addition, home cage behavior was measured both before and after drug administration. Inhibition of OCTs in the MH resulted in a reversible dose-dependent increase in extracellular 5-HT concentration. Increases in extracellular 5-HT concentrations were associated with increases in grooming behavior in rats treated with the highest concentration of decynium 22. No other behavioral responses were observed following administration of any concentration of decynium 22. These findings are consistent with the hypothesis that OCTs in the MH play an important role in the regulation of serotonergic neurotransmission and specific behavioral responses. Because the MH plays an important role in the neuroendocrine, autonomic, and behavioral responses to stress-related stimuli, these data lead to new questions regarding the role of interactions between corticosterone and corticosterone-sensitive OCTs in stress-induced 5-HT accumulation within the MH as well as the physiological and behavioral consequences of these interactions.
AB - In the rat dorsomedial hypothalamus (DMH), serotonin (5-HT) concentrations are altered rapidly in response to acute stressors. The mechanism for rapid changes in 5-HT concentrations in the DMH is not clear. We hypothesize that the mechanism involves corticosteroid-induced alterations in the uptake of 5-HT from extracellular fluid through the action of corticosterone-sensitive organic cation transporters (OCTs). To determine if OCTs affect the clearance of 5-HT from the extracellular fluid compartment within the medial hypothalamus (MH), the OCT blocker, decynium 22 (0, 10, 30, or 100 μM), was perfused into the MH via a microdialysis probe, and dialysate 5-HT concentrations were measured at 20 min intervals. In addition, home cage behavior was measured both before and after drug administration. Inhibition of OCTs in the MH resulted in a reversible dose-dependent increase in extracellular 5-HT concentration. Increases in extracellular 5-HT concentrations were associated with increases in grooming behavior in rats treated with the highest concentration of decynium 22. No other behavioral responses were observed following administration of any concentration of decynium 22. These findings are consistent with the hypothesis that OCTs in the MH play an important role in the regulation of serotonergic neurotransmission and specific behavioral responses. Because the MH plays an important role in the neuroendocrine, autonomic, and behavioral responses to stress-related stimuli, these data lead to new questions regarding the role of interactions between corticosterone and corticosterone-sensitive OCTs in stress-induced 5-HT accumulation within the MH as well as the physiological and behavioral consequences of these interactions.
KW - Corticosterone
KW - Dorsomedial hypothalamus
KW - HPA axis
KW - Organic cation transporter
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=27744531970&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27744531970&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2005.09.016
DO - 10.1016/j.brainres.2005.09.016
M3 - Article
C2 - 16266691
AN - SCOPUS:27744531970
VL - 1063
SP - 69
EP - 76
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -