RESUMEN
This study examined the effect of two high doses (3 or 6 mg/kg/day) of nicotine administrations via injections to pregnant rats on the dopaminergic, serotonergic, and noradrenergic systems in six brain regions in young adult male rats. The 3 mg/kg/day and 6 mg/kg/ day nicotine exposure resulted in significant decreases in dihydroxyphenylacetic acid (DOPAC) content in the neocortex and in both the neocortex and in the midbrain plus pons medulla, respectively, without any effects on the other brain regions such as the hypothalamus or striatum. No significant effects of prenatal nicotine were found on norepinephrine, serotonin, or 5-hydroxy-3-indolacetic acid levels. These data demonstrated that prenatal nicotine induced disturbances in the dopaminergic system in the young adult period. Furthermore, the region-specific reductions in the DOPAC content suggests that the exposure to a high dose of nicotine in utero might cause a predisposition to diseases related to a dopaminergic dysfunction in the frontal cortex.
Asunto(s)
Dopamina/metabolismo , Estimulantes Ganglionares/efectos adversos , Neocórtex/efectos de los fármacos , Nicotina/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Ácido 3,4-Dihidroxifenilacético/metabolismo , Análisis de Varianza , Animales , Conducta Animal/efectos de los fármacos , Monoaminas Biogénicas/metabolismo , Peso Corporal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Estimulantes Ganglionares/administración & dosificación , Masculino , Neocórtex/metabolismo , Nicotina/administración & dosificación , Embarazo , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
To assess the optimal dosing period and parameters for measurement of effects on male fertility, Compound T was administered to male Jcl:Wistar rats at dosage levels of 0, 2, 10 and/or 50 mg/kg/day for 4 weeks (Experiment 1) or for 9 weeks (Experiment 2). Experiment 1: In the 50 mg/kg group, the ventral prostate weight was low when compared to the control value, and desquamation of round spermatids was observed in the testes. Experiment 2: When treated males were mated with untreated females after dosing for 9 weeks (the first mating), the fertility index was slightly lowered and preimplantation loss was significantly elevated in the 50 mg/kg group as compared to the control values. In this treatment group, serum testosterone level at 2.5 hours after dosing was significantly decreased after dosing for 12 weeks, and degeneration of spermatids/spermatocytes in the testis and epididymis was observed after dosing for 13 weeks. After a recovery period of for 6 weeks, remating resulted in copulatory and fertility indices and cesarean section data which were comparable in all groups. In conclusion, there were no differences in toxicity relevant to male fertility between 4 and 9 weeks of dosing, and it is considered that the observed changes resulted from decreased function of Sertoli cells due to depressed production/secretion of testosterone.