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

• Published in: Psychopharmacologia Vol. 180; no. 2; pp. 316 - 326
• Main Authors: ZHUO CHEN, TETZLAFF, Julie, SRIPATHIRATHAN, Kumar, CARRASCO, Gonzalo A, SHANKARAN, Mahalakshmi, VAN DE KAR, Louis D, MUMA, Nancy A, BATTAGLIA, George
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.07.2005; Springer Nature B.V
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Adrenocorticotropic Hormone - blood; Adults; Animals; Biological and medical sciences; Cocaine; Cocaine - toxicity; Corticosterone - blood; Drug addictions; Emotional disorders; Female; Fetus - drug effects; Growth - drug effects; Hormones; Medical sciences; Mood disorders; Oxytocin - blood; Paroxetine - pharmacology; Piperazines - metabolism; Pregnancy; Prolactin - blood; Pyridines - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A - drug effects; Receptor, Serotonin, 5-HT1A - physiology; Renin - blood; Serotonin; Toxicology; Weight Gain - drug effects; Antidepressant; SSRIs; Psychotropic; Reuptake inhibitor; 8-OH-DPAT; Selective serotonin reuptake inhibitor; Prenatal; Ester; 5-HT1A Serotonine receptor; Piperidine derivatives; Development; Adult; Antidepressant agent; Drug of abuse; Human; Paroxetine; CNS stimulant; Serotonin; Neuroendocrine; Local anesthetic; Progeny; Chemotherapy; Treatment; Neurotransmitter; Cocaine
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-005-2249-8

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. 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. 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. 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. 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.