EXPOSURE TO THRESHOLD DOSES OF NICOTINE IN-UTERO .2. NEUROENDOCRINE RESPONSE TO NICOTINE IN ADULT MALE OFFSPRING

Groups of gravid female rats were injected subcutaneously with saline (SAL), a low-dose of nicotine (LN) (0.05 mg/kg, bid) or a high-dose of nicotine (HN) (3.0 mg/kg, bid) from day 4 to day 20 of gestation, or were left undisturbed. In adult 120-day-old male offspring, the ACTH and prolactin responses to acute nicotine challenge were evaluated. The experiment was performed on three separate occasions. Based upon dose-response and time-course studies with nicotine in normal animals, the neuroendocrine responses to nicotine (0.75 and 1.0 mg/kg, sc) were measured 7.5 min after nicotine administration, the peak response-time for both hormones. The ACTH response to acute nicotine administration was blunted significantly in the HN rats, but normal in the LN rats, for all three experiments. In two experiments, the prolactin response to acute nicotine administration was blunted significantly in the HN rats, but enhanced significantly in the LN offspring. The results indicate that prenatal nicotine administration can produce long-term neuroendocrine effects involving nicotinic-receptor coupled circuits, with long-term functional sequelae produced by dosages of nicotine considerably smaller than previously shown to be pharmacologically/toxicologically active.