Paroxetine is effective in desensitizing 5-HT1A receptor function in adult offspring exposed prenatally to cocaine

Zhuo Chen, Julie Tetzlaff, Kumar Sripathirathan, Gonzalo A. Carrasco, Mahalakshmi Shankaran, Louis D. Van De Kar, Nancy A. Muma, George Battaglia

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Rationale: Desensitization of postsynaptic 5-HT1A receptors may be responsible for the therapeutic effectiveness of serotonin selective uptake inhibitors (SSRIs). As prenatal cocaine exposure produces long-term deficits in 5-HT neurons in offspring, it may alter the ability of postsynaptic 5-HT 1A receptors to be desensitized by chronic paroxetine. Objectives: The aim of the study is to determine (1) prenatal cocaine-induced changes in 5-HT1A receptor function and (2) the effectiveness of chronic treatment with paroxetine to produce 5-HT1A receptor desensitization in adult offspring exposed to cocaine in utero. Methods: Pregnant rats received saline or (-)cocaine (15 mg/kg, s.c.) twice daily from gestational days 13 through 20. Adult male offspring from each of prenatal groups were treated with saline or paroxetine (10 mg/kg/day; i.p.) for 14 days. Eighteen hours post-treatment, rats were challenged with saline or the 5-HT1A receptor agonist (+)8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.04 or 0.2 mg/kg, s.c.). Plasma oxytocin, adrenocorticotropic hormone (ACTH), corticosterone, renin and prolactin were determined. Results: Prenatal cocaine exposure did not alter 5-HT1A receptor-mediated neuroendocrine responses. Paroxetine treatment desensitized 5-HT1A receptor-mediated increases in oxytocin, ACTH and corticosterone to a comparable extent in all offspring and reduced the E max for ACTH only in prenatal cocaine-exposed offspring. Cortical [3H]-8-OH-DPAT- or [ 3H]-WAY100635-labeled 5-HT1A receptors were unaltered by prenatal cocaine or subsequent paroxetine treatment. Conclusions: Postsynaptic 5-HT1A receptor function is unaltered by prenatal cocaine exposure and paroxetine can effectively desensitize 5-HT1A receptor function in adult cocaine-exposed offspring. These data suggest that paroxetine may be clinically effective in treating mood disorders in adults exposed in utero to cocaine.

Original languageEnglish (US)
Pages (from-to)316-326
Number of pages11
Issue number2
StatePublished - Jul 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology


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