5-Hydroxytryptamine2C Receptor Contribution to m-Chlorophenylpiperazine and N-Methyl-β-carboline-3-carboxamide-Induced Anxiety-Like Behavior and Limbic Brain Activation
| Autor: | Elizabeth A. Hackler, Elaine Sanders-Bush, Paul J. Gresch, Saikat Sengupta, John C. Gore, Greg H. Turner, Ariel Y. Deutch, Malcolm J. Avison |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Agonist medicine.medical_specialty Indoles medicine.drug_class Aminopyridines Anxiety Piperazines Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Limbic System Receptor Serotonin 5-HT2C medicine Animals Inverse agonist Prefrontal cortex Receptor Pharmacology Behavior Animal Receptor antagonist Magnetic Resonance Imaging Rats Serotonin Receptor Agonists Endocrinology nervous system Anxiogenic chemistry Serotonin 5-HT2 Receptor Antagonists Molecular Medicine Serotonin SB-242084 Neuroscience psychological phenomena and processes Carbolines |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 320:1023-1029 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | Activation of 5-hydroxytryptamine2C (5-HT(2C)) receptors by the 5-HT(2) receptor agonist m-chlorophenylpiperazine (m-CPP) elicits anxiety in humans and anxiety-like behavior in animals. We compared the effects of m-CPP with the anxiogenic GABA(A) receptor inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) on both anxiety-like behavior and regional brain activation using functional magnetic resonance imaging (fMRI) in the rat. We also determined whether the selective 5-HT(2C) receptor antagonist SB 242084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] would blunt m-CPP or FG-7142-induced neuronal activation. Both m-CPP (3 mg/kg i.p.) and FG-7142 (10 mg/kg i.p.) elicited anxiety-like behavior when measured in the social interaction test, and pretreatment with SB 242084 (1 mg/kg i.p.) completely blocked the behavioral effects of both anxiogenic drugs. Regional brain activation in vivo in response to anxiogenic drug challenge was determined by blood oxygen level-dependent (BOLD) fMRI using a powerful 9.4T magnet. Region of interest analyses revealed that m-CPP and FG-7142 significantly increased BOLD signals in brain regions that have been linked to anxiety, including the amygdala, dorsal hippocampus, and medial hypothalamus. These BOLD signal increases were blocked by pretreatment with SB 242084. In contrast, injection of m-CPP and FG-7142 resulted in BOLD signal decreases in the medial prefrontal cortex that were not blocked by SB 242084. In conclusion, the brain activation signals produced by anxiogenic doses of both m-CPP and FG-7142 are mediated at least partially by the 5-HT(2C) receptor, indicating that this receptor is a key component in anxiogenic neural circuitry. |
| Databáze: | OpenAIRE |
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