1-(m-Chlorophenyl)piperazine (mCPP) Dissociates In Vivo Serotonin Release from Long-Term Serotonin Depletion in Rat Brain

Baumann, Michael H.; Ayestas, Mario A.; Dersch, Christina M.; Rothman, Richard B.

doi:10.1016/s0893-133x(00)00221-9

Cited by 63 publications

(67 citation statements)

References 45 publications

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“…for surgical anesthesia. Indwelling jugular catheters made of Silastic Medical Grade tubing (Dow Corning, Midland, MI) were implanted into the right jugular vein and advanced to the atrium as described previously (Baumann et al, 2001). Immediately after catheter implantation, osmotic minipumps [Alzet model 2ML2 (14 days); Durect Corporation, Cupertino, CA] were inserted s.c. along the back, parallel to the spine, with the flow moderator pointing away from the incision.…”

Section: Animalsmentioning

confidence: 99%

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Chronic Fenfluramine Administration Increases Plasma Serotonin (5-Hydroxytryptamine) to Nontoxic Levels

Żółkowska

Baumann²,

Rothman³

2007

J Pharmacol Exp Ther

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Large elevations in blood serotonin (5-hydroxytryptamine; 5-HT) can produce valvular heart disease in humans and laboratory animals. In accordance, one prevailing hypothesis (i.e., the "5-HT hypothesis") suggests that 5-HT transporter substrates like fenfluramine increase the risk for valvular heart disease by elevating plasma 5-HT, secondary to the release of 5-HT from platelets. The main purpose of this study was to determine whether chronic administration of fenfluramine increases plasma 5-HT to concentrations that are associated with the development of valvular heart disease. To the best of our knowledge, this is the first study to address this issue using an in vivo microdialysis method that measures plasma 5-HT in nonhypoxic rats. We examined the effects of chronic (Ϯ)-fenfluramine and fluoxetine on plasma levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in blood samples from conscious catheterized rats. Plasma indoles were measured by high-performance liquid chromatography with electrochemical detection in the dialysates of whole blood. The baseline plasma 5-HT level was Ͻ1.0 nM. Chronic fenfluramine (14-day minipump infusion) produced small increases in baseline plasma 5-HT (ϳ2-4-fold), whereas chronic fluoxetine had no effect. Chronic fenfluramine and fluoxetine markedly decreased whole-blood 5-HT and reduced the ability of acute fenfluramine to evoke 5-HT release. Elevations in baseline plasma 5-HT produced by chronic fenfluramine are far below the micromolar levels necessary to produce valvular heart disease. Furthermore, chronic fenfluramine reduces the ability of acute fenfluramine to increase plasma 5-HT, suggesting that the 5-HT hypothesis cannot explain the increased risk of valvular heart disease in patients treated with fenfluramine.

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Section: Animalsmentioning

confidence: 99%

“…The brains were removed, and various brain regions were dissected on ice. Cortical monoamine concentrations were determined by HPLC-ECD as described previously (Baumann et al, 2001). Statistical Analyses.…”

Section: Animalsmentioning

confidence: 99%

Chronic Fenfluramine Administration Increases Plasma Serotonin (5-Hydroxytryptamine) to Nontoxic Levels

Żółkowska

Baumann²,

Rothman³

2007

J Pharmacol Exp Ther

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“…This study focuses on the effects of iontophoretically applied fenfluramine on the auditory responses of single IC neurons in a time frame of minutes. Although fenfluramine has often been infused locally into different brain regions (for example, Schwartz et al 1989;Consolo et al 1996;Baumann et al 2000Baumann et al , 2001Cobb and Abercrombie 2003;van der Stelt et al 2005), this study represents the first iontophoretic application of this drug, to our knowledge. In this study we measure the effects of fenfluramine on the auditory responses of single neurons, assess whether fenfluramine acts by releasing serotonin, and examine the distribution of different effects of fenfluramine relative to recording depth and characteristic frequency.…”

Section: Introductionmentioning

confidence: 95%

The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons

Hall

Hurley

2007

Hearing Research

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Local direct application of the neuromodulator serotonin strongly influences auditory response properties of neurons in the inferior colliculus (IC), but endogenous stores of serotonin may be released in a distinct spatial or temporal pattern. To explore this issue, the serotonin releaser fenfluramine was iontophoretically applied to extracellularly recorded neurons in the IC of the Mexican free-tailed bat (Tadarida brasiliensis). Fenfluramine mimicked the effects of serotonin on spike count and first spike latency in most neurons, and its effects could be blocked by co-application of serotonin receptor antagonists, consistent with fenfluramine-evoked serotonin release. Responses to fenfluramine did not vary during single applications or across multiple applications, suggesting that fenfluramine did not deplete serotonin stores. A predicted gradient in the effects of fenfluramine with serotonin fiber density was not observed, but neurons with fenfluramine-evoked increases in latency occurred at relatively greater recording depths compared to other neurons with similar characteristic frequencies. These findings support the conclusion that there may be spatial differences in the effects of exogenous and endogenous sources of serotonin, but that other factors such as the identities and locations of serotonin receptors are also likely to play a role in determining the dynamics of serotonergic effects.

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“…Furthermore, the selective 5-HT 2C serotonin receptor agonist 1-(3-chlorophenyl) piperazine (mCPP) has been reported to lower food intake and reduce the body weight by regulating energy dissipation (Vickers et al 2003) and to act as a 5-HT releaser itself (Bauman et al 2001). It may be suggested that a rapid increase of the induction of UCP1 mRNA in the BAT is associated with the activation of 5HT 1A and/or 5HT 2C receptors following the EtOH-induced 5-HT releases in the hypothalamus.…”

Section: Resultsmentioning

confidence: 99%

Effects of Ethanol on the Induction of Uncoupling Protein-1 (UCP1) mRNA in the Mouse Brown Adipose Tissue

Yoshimoto

Yasuhara

Kômura

et al. 2004

Tohoku J. Exp. Med.

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Expression of uncoupling protein-1 (UCP1) is increased by cold acclimation and overfeeding, and reduced in fasting and genetic obesity. It is known that the mitochondrial UCP1 in the brown adipose tissue (BAT) is an important key molecule for non-shivering thermogenesis. On the other hand, ethanol (EtOH) alters thermoregulation in humans and laboratory animals. However, the relationship between EtOH intake and UCP1 expression is not yet clear. Accordingly, the present study employed the technique of real-time quantitative polymerase-chain reaction (PCR) to investigate the effects of EtOH (0.5 or 2.0 g/kg) on the expression of UCP1 mRNA in the mouse BAT. Control mice were injected with the same volume of physiological saline intraperitoneally (IP). IP injection of EtOH (0.5 g/kg) caused a decrease and an increase of the expression of BAT UCP1 mRNA at 1 and 4 hours, respectively. Treatment with EtOH (2.0 g/kg) caused an increases of the expression of BAT UCP1 mRNA at both 2 and 4 hours. BAT UCP1 mRNA levels in both groups increased at 4 hours after EtOH administration. The levels of UCP1 mRNA returned to the control levels by 8 hours after EtOH administration. The expression of BAT UCP1 mRNA was upregulated following EtOH administration, although a lower dose of EtOH initially reduced the expression of UCP1 mRNA in BAT. These findings suggest that EtOH-induced UCP1 mRNA expression in BAT reflects an alteration of the set point of thermogenesis. uncoupling protein; ethanol; brown adipose tissue; mouse

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1-(m-Chlorophenyl)piperazine (mCPP) Dissociates In Vivo Serotonin Release from Long-Term Serotonin Depletion in Rat Brain

Cited by 63 publications

References 45 publications

Chronic Fenfluramine Administration Increases Plasma Serotonin (5-Hydroxytryptamine) to Nontoxic Levels

Chronic Fenfluramine Administration Increases Plasma Serotonin (5-Hydroxytryptamine) to Nontoxic Levels

The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons

Effects of Ethanol on the Induction of Uncoupling Protein-1 (UCP1) mRNA in the Mouse Brown Adipose Tissue

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