TY - JOUR
T1 - Desensitization of 5-HT1A receptors by 5-HT2A receptors in neuroendocrine neurons in vivo
AU - Zhang, Yahong
AU - Gray, Thackery S.
AU - D'Souza, Deborah N.
AU - Carrasco, Gonzalo A.
AU - Damjanoska, Katerina J.
AU - Dudas, Bertalan
AU - Garcia, Francisca
AU - Zainelli, Gina M.
AU - Sullivan Hanley, Nicole R.
AU - Battaglia, George
AU - Muma, Nancy A.
AU - Van De Kar, Louis D.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/7
Y1 - 2004/7
N2 - An imbalance between serotonin-2A (5-HT2A) and 5-HT1A receptors may underlie several mood disorders. The present studies determined whether 5-HT2A receptors interact with 5-HT1A receptors in the rat hypothalamic paraventricular nucleus (PVN). The sensitivity of the hypothalamic 5-HT1A receptors was measured as oxytocin and adrenocorticotropic hormone (ACTH) responses to the 5-HT1A receptor agonist (+)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide [(+)8-OH-DPA] (40 μg/kg s.c.). The 5-HT2A/2C receptor agonist (-)DOI [(-)-1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane HCI] (1 mg/kg s.c.) injected 2 h prior to (+)8-OH-DPAT significantly reduced the oxytocin and ACTH responses to (+)8-OH-DPAT, producing a heterologous desensitization of the 5-HT 1A receptors. Microinjection of the 5-HT2A receptor antagonist MDL100,907 [(+)-α-(2,3dimethoxyphenyl)-1-[2-(4- fluorophenylethyl)]-4-piperidinemethanol; 0, 10, or 20 nmol, 15 min prior to (-)DOI] into the PVN dose-dependently prevented the desensitization of 5-HT 1A receptors induced by the 5-HT2A receptor agonist (-)DOI. Double-label immunocytochemistry revealed a high degree of colocalization of 5-HT1A and 5-HT2A receptors in the oxytocin and corticotropin-releasing factor neurons of the PVN. Thus, activation of 5-HT2A receptors in the PVN may directly induce a heterologous desensitization of 5-HT1A receptors within individual neuroendocrine cells. These findings may provide insight into the long-term adaptation of 5-HT1A receptor signaling after changes in function of 5-HT 2A receptors; for example, during pharmacotherapy of mood disorders.
AB - An imbalance between serotonin-2A (5-HT2A) and 5-HT1A receptors may underlie several mood disorders. The present studies determined whether 5-HT2A receptors interact with 5-HT1A receptors in the rat hypothalamic paraventricular nucleus (PVN). The sensitivity of the hypothalamic 5-HT1A receptors was measured as oxytocin and adrenocorticotropic hormone (ACTH) responses to the 5-HT1A receptor agonist (+)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide [(+)8-OH-DPA] (40 μg/kg s.c.). The 5-HT2A/2C receptor agonist (-)DOI [(-)-1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane HCI] (1 mg/kg s.c.) injected 2 h prior to (+)8-OH-DPAT significantly reduced the oxytocin and ACTH responses to (+)8-OH-DPAT, producing a heterologous desensitization of the 5-HT 1A receptors. Microinjection of the 5-HT2A receptor antagonist MDL100,907 [(+)-α-(2,3dimethoxyphenyl)-1-[2-(4- fluorophenylethyl)]-4-piperidinemethanol; 0, 10, or 20 nmol, 15 min prior to (-)DOI] into the PVN dose-dependently prevented the desensitization of 5-HT 1A receptors induced by the 5-HT2A receptor agonist (-)DOI. Double-label immunocytochemistry revealed a high degree of colocalization of 5-HT1A and 5-HT2A receptors in the oxytocin and corticotropin-releasing factor neurons of the PVN. Thus, activation of 5-HT2A receptors in the PVN may directly induce a heterologous desensitization of 5-HT1A receptors within individual neuroendocrine cells. These findings may provide insight into the long-term adaptation of 5-HT1A receptor signaling after changes in function of 5-HT 2A receptors; for example, during pharmacotherapy of mood disorders.
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U2 - 10.1124/jpet.103.062224
DO - 10.1124/jpet.103.062224
M3 - Article
C2 - 15064330
AN - SCOPUS:4344662295
SN - 0022-3565
VL - 310
SP - 59
EP - 66
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -