Absence of Thermal Hyperalgesia in Serotonin Transporter-Deficient Mice

Vogel, Carola; Mößner, Rainald; Gerlach, Manfred; Heinemann, Thoralf; Murphy, Dennis L.; Riederer, Peter; Lesch, Klaus‐Peter; Sommer, Claudia

doi:10.1523/jneurosci.23-02-00708.2003

Cited by 108 publications

(78 citation statements)

References 45 publications

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“…In addition, 5-HTT null mutant mice have been found to show abnormalities in reward-related and locomotor responses to psychostimulants Uhl et al, 2002), analgesic responses (Vogel et al, 2003), and REM sleep (Wisor et al, 2003). In the present study, 5-HTT null mutant mice were characterized for anxiety-related behaviors using a battery of tests (ie elevated plus maze, light2dark exploration test, emergence test, and open field test), as previously described (Holmes et al, 2003).…”

Section: Introductionmentioning

confidence: 90%

Mice Lacking the Serotonin Transporter Exhibit 5-HT1A Receptor-Mediated Abnormalities in Tests for Anxiety-like Behavior

Holmes

Yang

Lesch

et al. 2003

Neuropsychopharmacol

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The serotonin transporter (5-HTT) regulates serotonergic neurotransmission via clearance of extracellular serotonin. Abnormalities in 5-HTT expression or function are found in mood and anxiety disorders, and the 5-HTT is a major target for antidepressants and anxiolytics. The 5-HTT is further implicated in the pathophysiology of these disorders by evidence that genetic variation in the promoter region of the HTT (SLC6A4) is associated with individual differences in anxiety and neural responses to fear. To further evaluate the role of the 5-HTT in anxiety, we employed a mouse model in which the 5-HTT gene (htt) was constitutively inactivated. 5-HTT À/À mice were characterized for anxiety-related behaviors using a battery of tests (elevated plus maze, light2dark exploration test, emergence test, and open field test). Male and female 5-HTT À/À mice showed robust phenotypic abnormalities as compared to +/+ littermates, suggestive of increased anxiety-like behavior and inhibited exploratory locomotion. The selective 5-HT 1A receptor antagonist, WAY 100635 (0.05-0.3 mg/kg), produced a significant anxiolytic-like effect in the elevated plus maze in 5-HTT À/À mice, but not +/+ controls. The present findings demonstrate abnormal behavioral phenotypes in 5-HTT null mutant mice in tests for anxiety-like and exploratory behavior, and suggest a role for the 5-HT 1A receptor in mediating these abnormalities. 5-HTT null mutant mice provide a model to investigate the role of the 5-HTT in mood and anxiety disorders.

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Section: Introductionmentioning

confidence: 90%

Mice Lacking the Serotonin Transporter Exhibit 5-HT1A Receptor-Mediated Abnormalities in Tests for Anxiety-like Behavior

Holmes

Yang

Lesch

et al. 2003

Neuropsychopharmacol

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285

203

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“…Culture media kept for 5 days in the same incubator in the absence of cells was used as negative control. Samples were sonicated under argon in ice-cold H 3 PO 4 (150 mM) and diethylenetriamine pentaacetic acid (500 mM), centrifuged at 35 000 g for 20 min at 41C, as described previously (Vogel et al, 2003). Briefly, the supernatant was filtered through Millipore (Bedford) Ultrafree-MC filter cups at 9000 g for 1-2 h at 41C.…”

Section: Determination Of 5-ht and 5-hydroxyindolacetic Acid (5-hiaa)mentioning

confidence: 99%

Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

Benninghoff¹,

Gritti²,

Rizzi³

et al. 2009

Neuropsychopharmacol

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Serotonin (5-HT) and the serotonergic system have recently been indicated as modulators of adult hippocampal neurogenesis. In this study, we evaluated the role of 5-HT on the functional features in neurospheres derived from adult neural stem cells (ANSC). We cultured neurospheres derived from mouse hippocampus in serum-free medium containing epidermal (EGF) and type-2 fibroblast growth factor (FGF2). Under these conditions ANSC expressed both isoforms of tryptophane-hydroxylase (TPH) and produced 5-HT. Blocking TPH function by para-chlorophenylalanine (PCPA) reduced ANSC proliferation, which was rescued by exogenous 5-HT. 5-HT action on ANSC was mediated predominantly by the serotonin receptor subtype 5-HT1A and, to a lesser extent, through the 5-HT2C (receptor) subtype, as shown by selectively antagonizing these receptors. Finally, we documented a 5-HT-induced increase of ANSC migration activity. In summary, we demonstrated a powerful serotonergic impact on ANSC functional features, which was mainly mediated by 5-HT1A receptors.

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“…The lack of effect on mechanical allodynia is surprising, and we currently have no explanation for this observation. However, differences between development of heat hyperalgesia and mechanical allodynia, or effects of drugs on heat hyperalgesia and mechanical allodynia, have been observed in numerous studies (Meller et al, 1993;Ossipov et al, 1999;Caterina et al, 2000;Sluka, 2002;Neubert et al, 2003;Vogel et al, 2003;Walker et al, 2003). Activation of ionotropic NMDA receptors alone in the spinal cord produces thermal hyperalgesia, but coactivation of ionotropic AMPA and metabotropic glutamate receptors is required to produce mechanical allodynia (Meller et al, 1993).…”

mentioning

confidence: 99%

Acetazolamide, a Carbonic Anhydrase Inhibitor, Reverses Inflammation-Induced Thermal Hyperalgesia in Rats

Radhakrishnan

Sluka²

2005

J Pharmacol Exp Ther

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Inflammatory pain is linked to reduction in tissue pH. Tissue proton generation is mainly mediated by carbonic anhydrases (CAs). We therefore hypothesized that inhibition of CAs with acetazolamide (ACTZ) increases the tissue pH and reverses inflammation-induced pain. CAs are also present in the central nervous system and control anion concentrations. Furthermore, ACTZ has direct effects on ion channels involved in nociception. In the current study, responses to heat and mechanical stimuli (von Frey filaments) of the paw were assessed before and after carrageenan-induced muscle inflammation and after treatment with ACTZ in rats. ACTZ was administered systemically, locally, or intrathecally 24 h after the induction of inflammation. In separate studies, pH was measured in the inflamed and noninflamed muscles and after administration of ACTZ. Carrageenan injection to the gastrocnemius muscle produced heat hyperalgesia and mechanical allodynia of the paw. Systemic ACTZ reversed the heat hyperalgesia but not mechanical allodynia. Similarly, injections of ACTZ into the inflamed muscle or intrathecally reversed the heat hyperalgesia but not mechanical allodynia. Surprisingly, the pH in the inflamed muscle was not reduced compared with noninflamed muscle. Thus, the current data do not support our hypothesis that ACTZ reduces inflammatory hyperalgesia by raising the reduced pH in muscle. Although the possibility of pH changes and the role of CAs in the microenvironment cannot be ruled out, the mechanism of ACTZ-induced antihyperalgesia is not clear from this study. It is possible that the inhibition of ion channels and/or the inhibition of spinally located CAs contribute to the observed antihyperalgesia.

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Absence of Thermal Hyperalgesia in Serotonin Transporter-Deficient Mice

Cited by 108 publications

References 45 publications

Mice Lacking the Serotonin Transporter Exhibit 5-HT1A Receptor-Mediated Abnormalities in Tests for Anxiety-like Behavior

Mice Lacking the Serotonin Transporter Exhibit 5-HT1A Receptor-Mediated Abnormalities in Tests for Anxiety-like Behavior

Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

Acetazolamide, a Carbonic Anhydrase Inhibitor, Reverses Inflammation-Induced Thermal Hyperalgesia in Rats

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