Prenatal cocaine exposure potentiates paroxetine-induced desensitization of 5-HT2A receptor function in adult male rat offspring

Zhuo Chen, Kate Waimey, Louis D. Van De Kar, Gonzalo A. Carrasco, Michelle Landry, George Battaglia

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

This study investigated the ability of prenatal exposure to cocaine to alter serotonin2A (5-HT2A) receptor function and paroxetine-induced desensitization of 5-HT2A receptor function in rat offspring. Following exposure to saline or (-)cocaine (15 mg/kg, s.c., b.i.d.), during gestational days 13-20, adult male offspring were treated with either saline or paroxetine (10 mg/kg/day, i.p. 14 days). Eighteen hours post-treatment, changes in the stimulation of oxytocin, adrenocorticotropic hormone (ACTH) and corticosterone by (-)4-iodo-2,5-dimethoxyphenylisopropylamine (DOI, 0.5 or 2.0 mg/kg, s.c.) and in 5-HT2A receptor densities were determined. Prenatal cocaine exposure did not alter 5-HT2A receptor-mediated neuroendocrine responses or 5-HT2A receptor densities. In contrast, paroxetine treatment reduced cortical 5-HT2A receptors (18-25%) and desensitized 5-HT2A receptor-mediated oxytocin responses in both offspring groups. Furthermore, in cocaine offspring, paroxetine produced an inhibition of 5-HT2A receptor-mediated increase in plasma ACTH levels and a greater attenuation of the oxytocin responses to (-)DOI. Paroxetine-induced reductions in body weight gain (-8.8%) were comparable in both offspring groups. These data, demonstrating that prenatal exposure to cocaine potentiates paroxetine-induced desensitization of 5-HT2A receptor function, may be clinically relevant with respect to treating mood disorders in adults exposed in utero to cocaine.

Original languageEnglish (US)
Pages (from-to)942-953
Number of pages12
JournalNeuropharmacology
Volume46
Issue number7
DOIs
StatePublished - Jun 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

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