Faculty Collaboration Database

Paroxetine is effective in desensitizing 5-HT1A receptor function in adult offspring exposed prenatally to cocaine. Psychopharmacology (Berl) 2005 Jul;180(2):316-26

Date

05/03/2005

Pubmed ID

15864558

DOI

10.1007/s00213-005-2249-8

Scopus ID

2-s2.0-21344467460 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

RATIONALE: Desensitization of postsynaptic 5-HT(1A) 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-HT(1A) receptor function and (2) the effectiveness of chronic treatment with paroxetine to produce 5-HT(1A) 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-HT(1A) 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-HT(1A) receptor-mediated neuroendocrine responses. Paroxetine treatment desensitized 5-HT(1A) 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 [(3)H]-8-OH-DPAT- or [(3)H]-WAY100635-labeled 5-HT(1A) receptors were unaltered by prenatal cocaine or subsequent paroxetine treatment.

CONCLUSIONS: Postsynaptic 5-HT(1A) receptor function is unaltered by prenatal cocaine exposure and paroxetine can effectively desensitize 5-HT(1A) 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.

Author List

Chen Z, Tetzlaff J, Sripathirathan K, Carrasco GA, Shankaran M, Van De Kar LD, Muma NA, Battaglia G

MESH terms used to index this publication - Major topics in bold

8-Hydroxy-2-(di-n-propylamino)tetralin
Adrenocorticotropic Hormone
Animals
Cocaine
Corticosterone
Female
Fetus
Growth
Oxytocin
Paroxetine
Piperazines
Pregnancy
Prolactin
Pyridines
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1A
Renin
Weight Gain