Potentiation of 5-HT1A receptor-mediated neuroendocrine responses in male but not female rat progeny after prenatal cocaine: evidence for gender differences.
The present study investigated the consequences of prenatal cocaine exposure on central serotonin (5-HT) 5-HT1A receptor-mediated function in prepubescent male and female progeny. Pregnant rats received saline or cocaine (15 mg/kg s.c.) twice daily from gestational day 13 through 20. All litters were fostered to nontreated lactating dams. Cocaine did not alter weight gain during pregnancy and did not affect progeny weight at birth or at postnatal day 28. Male and female progeny were tested at a prepubescent age (postnatal day 28) by measuring 1) the stimulation of adrenocorticotropic hormone, corticosterone and renin by a maximally effective dose (0.5 mg/kg s.c.) of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT); and 2) [3H]8-OH-DPAT-labeled 5-HT1A receptors and [3H]paroxetine-labeled 5-HT uptake sites in hypothalamus, cortex and midbrain. Basal hormone levels were unaffected by prenatal cocaine exposure. However, prenatal cocaine exposure significantly potentiated the adrenocorticotropic hormone (+28%) and renin (+53%) responses to 8-OH-DPAT in male but not female progeny. In contrast, the corticosterone response to 8-OH-DPAT was not significantly altered in either male or female progeny. Likewise, the number of 5-HT1A receptors and 5-HT uptake sites in the cortex, midbrain and hypothalamus were unaffected by prenatal cocaine exposure. These data demonstrate that prenatal cocaine exposure can potentiate brain 5-HT1A receptor-mediated function in progeny and that alterations in hypothalamic 5-HT1A function are gender specific. These data suggest the possibility that prenatal cocaine may increase 5-HT1A receptor function in extrahypothalamic brain regions.
Battaglia
G
G
Department of Pharmacology and Experimental Therapeutics, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois.
Cabrera
T M
TM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D003345:Corticosterone / Q000097:blood; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012083:Renin / Q000097:blood; D012701:Serotonin / Q000378:metabolism; D012737:Sex Factors
D011985:Receptors, Serotonin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone; D012083:Renin; D003042:Cocaine; D003345:Corticosterone