5-HT1A receptors mediate (+)8-OH-DPAT-stimulation of extracellular signal-regulated kinase (MAP kinase) in vivo in rat hypothalamus: Time dependence and regional differences

James W. Crane, Keiko Shimizu, Gonzalo A. Carrasco, Francisca Garcia, Cuihong Jia, Nicole R. Sullivan, Deborah N. D'Souza, Yahong Zhang, Louis D. Van de Kar, Nancy A. Muma, George Battaglia

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Abstract

Brain serotonin 1A (5-HT1A) receptors play an important role in mood disorders and can modulate various intracellular signaling mechanisms. We previously reported that systemic administration of either full or partial 5-HT1A agonists increases neuroendocrine responses and that tandospirone, an azapirone partial agonist, can activate (phosphorylate) extracellular signal-regulated kinase (ERK) in the hypothalamic paraventricular nucleus (PVN). In contrast, decreased levels of phosphoERK (pERK) have been reported in hippocampus following in vivo administration of either azapirone or aminotetralin 5-HT1A agonists, such as 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT). The present study investigated the time-dependent activation of MAP kinase in hypothalamus by (+)8-OH-DPAT to determine the regional differences and receptor specificity of the changes in pERK. Adult male rats received a systemic injection of (+)8-OH-DPAT (200 μg/kg, s.c.). The time-dependent changes in ERK activation were examined in hypothalamic nuclei as well as other brain regions associated with modulation of mood. (+)8-OH-DPAT produced a rapid increase (at 5 min) and transient return (at 15 min) of pERK levels in PVN and medial basal hypothalamus. In contrast, pERK levels in hippocampus were reduced at both 5 and 15 min after (+)8-OH-DPAT. Pretreatment with the 5-HT1A receptor-specific antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY100635) completely blocked the (+)8-OH-DPAT-mediated changes in pERK levels in PVN, medial basal hypothalamus, and hippocampus. No significant (+)8-OH-DPAT-induced changes in pERK were observed in dorsal raphe or amygdala. In conclusion, these results demonstrate that 8-OH-DPAT activation of MAP kinase signaling in vivo is a transient and region-specific phenomenon and in rat hypothalamus and hippocampus is mediated by 5-HT1A receptors.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalBrain Research
Volume1183
Issue number1
DOIs
StatePublished - Dec 5 2007

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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    Crane, J. W., Shimizu, K., Carrasco, G. A., Garcia, F., Jia, C., Sullivan, N. R., D'Souza, D. N., Zhang, Y., Van de Kar, L. D., Muma, N. A., & Battaglia, G. (2007). 5-HT1A receptors mediate (+)8-OH-DPAT-stimulation of extracellular signal-regulated kinase (MAP kinase) in vivo in rat hypothalamus: Time dependence and regional differences. Brain Research, 1183(1), 51-59. https://doi.org/10.1016/j.brainres.2007.07.101