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

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Abstract

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-HT1A 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 Emax 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.

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Acknowledgements

The authors thank Kate Waimey, Francisca Garcia, and Julia Hunt for their assistance with some aspects of this study. We also thank Dr. James Sinacore for helpful discussions and providing expertise on the statistical analyses of the data.

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Authors and Affiliations

  1. Department of Pharmacology and Center for Serotonin Disorders Research, Stritch School of Medicine, Loyola University of Chicago, 2160 South First Avenue, Maywood, IL, 60153, USA

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

  2. Department of Pharmacology and Experimental Therapeutics, Stritch School of Medicine, Loyola University of Chicago, 2160 South First Avenue, Maywood, IL, 60153, USA

    George Battaglia

Authors
  1. Zhuo Chen
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  2. Julie Tetzlaff
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  3. Kumar Sripathirathan
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  4. Gonzalo A. Carrasco
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  5. Mahalakshmi Shankaran
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  6. Louis D. Van De Kar
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  7. Nancy A. Muma
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  8. George Battaglia
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Corresponding author

Correspondence to George Battaglia.

Additional information

This study was supported by United States Public Health Services grants DA07741 (G.B.) and DA13669 (L.VDK.)

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Chen, Z., Tetzlaff, J., Sripathirathan, K. et al. Paroxetine is effective in desensitizing 5-HT1A receptor function in adult offspring exposed prenatally to cocaine. Psychopharmacology 180, 316–326 (2005). https://doi.org/10.1007/s00213-005-2249-8

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  • DOI: https://doi.org/10.1007/s00213-005-2249-8

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