Repeated Swim Impairs Serotonin Clearance via a Corticosterone-Sensitive Mechanism: Organic Cation Transporter 3, the Smoking Gun

Baganz, Nicole L.; Horton, Rebecca E.; Martin, Kathryn P.; Holmes, Andrew; Daws, Lynette C.

doi:10.1523/jneurosci.2740-10.2010

Cited by 67 publications

(50 citation statements)

References 75 publications

(119 reference statements)

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“…Consistent with our published findings in wild-type C57Bl/6 mice (Montañez et al, 2003; Baganz et al, 2010), fluvoxamine inhibited 5-HT clearance time in 5-HT 1B +/+ mice (T 80 pre-fluvoxamine 84 ± 8 s, vs 2 min post-fluvoxamine 110 ± 8 s, t 5 = 4.61, P < 0.01). Similarly, fluvoxamine inhibited 5-HT clearance time in 5-HT 1B +/− mice (pre- 75 ± 15s vs post- 106 ± 15s, t 5 = 3.28, P < 0.05) and 5-HT 1B −/− mice (pre- 104 ± 36 s vs post- 160 ± 41 s, t 4 = 6.27, P < 0.01).…”

Section: 0 Resultssupporting

confidence: 91%

5-HT1B receptor modulation of the serotonin transporter in vivo: Studies using KO mice

Montañez

Munn

Owens

et al. 2014

Neurochemistry International

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The serotonin transporter (SERT) controls the strength and duration of serotonergic neurotransmission by the high-affinity uptake of ser otonin (5-HT) from extracellular fluid. SERT is a key target for many psychotherapeutic and abused drugs, therefore understanding how SERT activity and expression are regulated is of fundamental importance. A growing literature suggests that SERT activity is under regulatory control of the 5-HT1B autoreceptor. The present studies made use of mice with a constitutive reduction (5-HT1B+/−) or knockout of 5-HT1B receptors (5-HT1B−/−), as well as mice with a constitutive knockout of SERT (SERT−/−) to further explore the relationship between SERT activity and 5-HT1B receptor expression. High-speed chronoamperometry was used to measure clearance of 5-HT from CA3 region of hippocampus in vivo. Serotonin clearance rate, over a range of 5-HT concentrations, did not differ among 5-HT1B receptor genotypes, nor did [3H]cyanoimipramine binding to SERT in this brain region, suggesting that SERT activity is not affected by constitutive reduction or loss of 5-HT1B receptors; alternatively, it might be that other transport mechanisms for 5-HT compensate for loss of 5-HT1B receptors. Consistent with previous reports, we found that the 5-HT1B receptor antagonist, cyanopindolol, inhibited 5-HT clearance in wild-type mice. However, this effect of cyanopindolol was lost in 5-HT1B−/− mice and diminished in 5-HT1B+/− mice, indicating that the 5-HT1B receptor is necessary for cyanopindolol to inhibit 5-HT clearance. Likewise, cyanopindolol was without effect on 5-HT clearance in SERT−/− mice, demonstrating a requirement for the presence of both SERT and 5-HT1B receptors in order for cyanopindolol to inhibit 5-HT clearance in CA3 region of hippocampus. Our findings are consistent with SERT being under the regulatory control of 5-HT1B autoreceptors. Future studies to identify signaling pathways involved may help elucidate novel therapeutic targets for the treatment of psychiatric disorders, particularly those linked to gene variants of the 5-HT1B receptor.

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Section: 0 Resultssupporting

confidence: 91%

5-HT1B receptor modulation of the serotonin transporter in vivo: Studies using KO mice

Montañez

Munn

Owens

et al. 2014

Neurochemistry International

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“…Finally, we cannot rule out the possibility that, as observed with SSRIs, corticosterone decreased 5-HT reuptake. In line with this hypothesis, a recent study has shown that corticosterone blocks the reuptake of 5-HT through low-affinity monoamine transporters (Baganz et al, 2010). This point should draw our attention for future investigations.…”

Section: Resultssupporting

confidence: 56%

Functional Status of Somatodendritic Serotonin 1A Autoreceptor after Long-Term Treatment with Fluoxetine in a Mouse Model of Anxiety/Depression Based on Repeated Corticosterone Administration

Rainer¹,

Nguyen²,

Quesseveur³

et al. 2011

Mol Pharmacol

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Most preclinical studies investigating the effects and the mechanism of action of antidepressants have been performed in naive rodents. This is inappropriate because antidepressants act on specific symptoms of the pathological condition, such as distress and anxiety. We have developed a mouse model of anxiety/depression based on addition of corticosterone to drinking water. This model is highly reproducible and easy to set up compared with unpredictable chronic mild stress. The serotonin 1A (5-HT 1A ) autoreceptor is known to play a role in mood disorders and their treatments. An increase in somatodendritic 5-HT 1A autoreceptor density in the dorsal raphe (DR) attenuates the therapeutic activity of selective serotonin-reuptake inhibitors (SSRIs), whereas their functional desensitization promotes activation of brain serotonergic transmission, thereby representing an adaptive change relevant to their therapeutic effect. Here we assessed the effects of sustained administration of the SSRI fluoxetine on 5-HT 1A autoreceptor sensitivity in mice administered with corticosterone. Fluoxetine attenuated hypothermia induced by the 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin, decreased DR 5-HT neuronal activity, and decreased 5-HT release in both vehicle-and corticosterone-pretreated mice. However, such desensitization was more pronounced in corticosterone-pretreated mice. This change had an overall effect on serotonergic tone because we found a greater firing rate of 5-HT neurons associated with an enhancement of 5-HT outflow in the DR of corticosterone-pretreated mice in response to fluoxetine compared with the corresponding group of vehicle-pretreated mice. These results provide cellular explanations for the antidepressant effects produced by SSRIs in subjects with pathological conditions but not in naive animals or healthy volunteers.

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“…Given this, it is interesting that CORT blocks ancillary transporters of 5-HT (i.e. “uptake 2”) such as organic cation transporters (OCTs) from clearing extracellular 5-HT in the brain (Baganz et al, 2010; Hill et al, 2011). This lends support to the hypothesis that their blockade may be a useful strategy for treating sociability deficits, warranting further studies in this area.…”

Section: Discussionmentioning

confidence: 99%

Acute dietary tryptophan manipulation differentially alters social behavior, brain serotonin and plasma corticosterone in three inbred mouse strains

et al. 2015

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Clinical evidence indicates brain serotonin (5-HT) stores and neurotransmission may be inadequate in subpopulations of individuals with autism, and this may contribute to characteristically impaired social behaviors. Findings that depletion of the 5-HT precursor tryptophan (TRP) worsens autism symptoms support this hypothesis. Yet dietetic studies show and parents report that many children with autism consume less TRP than peers. To measure the impact of dietary TRP content on social behavior, we administered either diets devoid of TRP, with standard TRP (0.2 gm%), or with 1% added TRP (1.2 gm%) overnight to three mouse strains. Of these, BTBRT+Itpr3tf/J and 129S1/SvImJ consistently exhibit low preference for social interaction relative to C57BL/6. We found that TRP depletion reduced C57BL/6 and 129S social interaction preference, while TRP enhancement improved BTBR sociability (p < 0.05; N= 8–10). Subsequent marble burying was similar regardless of grouping. After behavior tests, brain TRP levels and plasma corticosterone were higher in TRP enhanced C57BL/6 and BTBR, while 5-HT levels were reduced in all strains by TRP depletion (p <0.05; N= 4 −10). Relative hyperactivity of BTBR and hypoactivity of 129S, evident in self-grooming and chamber entries during sociability tests, were uninfluenced by dietary TRP. Our findings demonstrate mouse sociability and brain 5-HT turnover are reduced by acute TRP depletion, and can be enhanced by TRP supplementation. This outcome warrants further basic and/or clinical studies employing biomarker combinations such as TRP metabolism and 5-HT regulated hormones to characterize the conditions wherein TRP supplementation can best ameliorate sociability deficits.

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Repeated Swim Impairs Serotonin Clearance via a Corticosterone-Sensitive Mechanism: Organic Cation Transporter 3, the Smoking Gun

Cited by 67 publications

References 75 publications

5-HT1B receptor modulation of the serotonin transporter in vivo: Studies using KO mice

5-HT1B receptor modulation of the serotonin transporter in vivo: Studies using KO mice

Functional Status of Somatodendritic Serotonin 1A Autoreceptor after Long-Term Treatment with Fluoxetine in a Mouse Model of Anxiety/Depression Based on Repeated Corticosterone Administration

Acute dietary tryptophan manipulation differentially alters social behavior, brain serotonin and plasma corticosterone in three inbred mouse strains

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