Comparative effects of maternal prenatal and postnatal exposures to astemizole on reproductive parameters of rats.
The prenatal and postnatal effects of administration of a nonsedative antihistamine H1, astemizole (ATZ), were compared. ATZ (10 mg/kg) was injected daily into female Wistar rats throughout pregnancy (prenatal treatment) or during the first 6 days of lactation (postnatal treatment). Neither treatment modified dam body weight. Prenatal exposure reduced offspring body weight and lead to a latter expression of the vaginal opening of female offspring. In addition, a long-term disruption of male reproductive behavior was observed, while female sexual behavior was not modified. The sexual activity index and the intromission frequency were increased in prenatally treated animals. Testes wet weight was reduced, but no modifications were detected in vas deferens or seminal vesicles. Postnatal treatment did not alter offspring body weight, open-field activity, sexual behavior and organ weight as well as did not delay testes descent but reduced the time until vaginal opening. Hypothalamic serotonin (5-HT), dopamine (DA) and noradrenaline (NA) as well as DA and NA metabolites were not modified by both prenatal and postnatal treatments. Increased striatal 3,4-dihydroxyphenylacetic acid (DOPAC) levels were observed after prenatal and postnatal treatments, while only postnatal 5-HT levels were increased. We propose that the present results indicate that prenatal ATZ exposure can have long-lasting organizational effects on reproductive behavior of male rats, while postnatal exposure to this drug did not alter mating behavior. In relation to female rats, prenatal and postnatal exposures to ATZ accelerated puberty but did not alter sexual behavior. Neurochemical data show that both treatments increased striatal dopaminergic system activity, suggesting a central ATZ effect after perinatal exposure.
Almeida
R G
RG
Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, cep: 05508-900, São Paulo, SP, Brazil.
Florio
J C
JC
Spinosa
H S
HS
Bernardi
M M
MM
D000818:Animals; D016589:Astemizole / Q000633:toxicity*; D001479:Basal Ganglia / Q000378:metabolism; D015306:Biogenic Monoamines / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006634:Histamine H1 Antagonists / Q000633:toxicity*; D007031:Hypothalamus / Q000378:metabolism; D007774:Lactation; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D051381:Rats; D012737:Sex Factors; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D012741:Sexual Maturation / Q000187:drug effects
D015306:Biogenic Monoamines; D006634:Histamine H1 Antagonists; D016589:Astemizole