ABSTRACT
Pregnant female Sprague-Dawley rats were injected once daily with either 40 mg/kg cocaine hydrochloride or 0.9% saline from gestation day (GD)12 to GD 21. On postnatal day (PND)30, male offspring were sacrificed and fresh tissue from the striatum (ST) and nucleus accumbens (NA) was dissected for assessment of dopamine (DA) receptor affinity, DA uptake and DA release. 10-6 M cocaine inhibited [3H]-DA uptake in ST tissue, whereas 10-4 and 10-5 M cocaine inhibited [3H]-DA uptake in the NA tissue of postnatally exposed cocaine offspring verses saline-treated controls (p <0.05). DA release stimulated by 10-6 M amphetamine was significantly reduced in both the ST (p <0.001) and NA (p <0.01) of postnatal offspring exposed to cocaine in utero compared with saline controls. In utero cocaine exposure did not influence offspring ST or NA dopamine 1 (D1) dissociation constant (Kd) or receptor density (Bmax). However, the treatment group experienced a significant increase of binding affinity for the ST D2 receptor with no change in D2 Bmax. The treatment group also experienced no change in D2 receptor binding affinity or number of binding sites in the NA. These results show that in utero exposure to cocaine results in altered postnatal dopaminergic function.
ABSTRACT
Pregnant female Sprague-Dawley rats were injected with either 40 mg/kg (-)cocaine hydrochloride or an equivalent volume of 0.9% saline, subcutaneously (s.c.), once daily from gestational day 12 (GD 12) to GD 21. Gestational cocaine exposure had no effect on maternal weight gain, length of gestation, birthweight, fetal mortality, postnatal weight gain or locomotive activity in offspring. There was an unusual reduction in the male/female offspring ratio in the treated group (1:0.65) verses controls (1:1.04) (p <0.01). Male offspring scored significantly lower on memory and learning tasks on postnatal day 30 (PND30) as determined by the water maze test (p <0.01). Exposure to cocaine in utero had no effect on postnatal female sexual maturation or cognitive function. The present study indicates that gestational cocaine exposure can lead to cognitive impairment selectively in male offspring, without any apparent postnatal physical abnormalities or adverse effects on maternal health status.
ABSTRACT
Female pregnant Sprague-Dawley rats were injected once daily with 40 mg/kg cocaine hydrochloride or 0.9% saline from gestational day 12 (GD 12) to GD 21. From postnatal day 21 (PND 21) to PND 60, both male and female offspring were examined for stress response. Treated male and female offspring demonstrated a diminished tolerance to stress as determined by a cold water stress test performed at PND 21, 30 and 40. Base hormonal levels of adrenocorticotropin hormone (ACTH) and corticosterone were not affected by prenatal cocaine exposure in male offspring at PND 30. However, immobilization for 1 hr caused a significant sustained elevation of corticosterone levels at both PND 30 and PND 60 in male treated offspring as compared to the control group. Plasma ACTH levels were also significantly sustained after 1 hr of immobilization at PND 60 for the cocaine-treated male offspring. These results indicate both a diminished capacity to respond to stress and an abnormal heightened reactivity of the pituitary-adrenal axis in offspring exposed to cocaine in utero.
