Cocaine-mediated supersensitivity of 5-HT2A receptors in hypothalamic paraventricular nucleus is a withdrawal-induced phenomenon

G. A. Carrasco, L. D. Van de Kar, N. R. Sullivan, M. Landry, F. Garcia, N. A. Muma, G. Battaglia

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15 Scopus citations


We previously reported that treatment and withdrawal from cocaine increases: (1) 5-HT2A receptor-mediated neuroendocrine responses, and (2) Gαq and Gα11 G-protein levels in the hypothalamic paraventricular nucleus (PVN) at 48 h post-treatment. This study investigates changes in the initial 24 h of withdrawal to discern whether 5-HT2A receptor supersensitivity is due to cocaine treatment or is induced during the withdrawal period. We report here increases in 5-HT2A receptor-mediated neuroendocrine responses only 12 or 24 h post-treatment, but not during the initial 4 h withdrawal period. Levels of membrane- or cytosol-associated Gαq or Gα11 proteins in PVN are not altered during the first 24 h of withdrawal. However, the density of 125I-(-)-1-(2,5 dimethoxy-4-iodophenyl)-2-amino-propane HCl (DOI)-labeled high-affinity 5-HT2A receptors in PVN increased 35% in rats withdrawn from cocaine for 24 h. These findings demonstrate that cocaine-induced increases in 5-HT2A receptor function in PVN represents a withdrawal-induced phenomena that: (1) is likely attributed to increased G-protein coupled/high-affinity conformational state of the 5-HT2A receptor, and (2) occurs in the absence of changes in the levels of associated G proteins during the first 24 h.

Original languageEnglish (US)
Pages (from-to)7-13
Number of pages7
Issue number1
StatePublished - Nov 17 2006

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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