Exposure to threshold doses of nicotine in utero: I. Neuroendocrine response to restraint stress in adult male offspring.

Gravid female rats were injected subcutaneously with saline or nicotine (3.0 mg/kg and 0.05 mg/kg, bid) from day 4 to day 20 of gestation or were left undisturbed. In adult 120-day old male offspring, the ACTH, corticosterone and prolactin concentrations before, during (15, 30, 45 and 60 minutes) and after (30, 60, 90 and 120 minutes) one hour of restraint stress were studied. Baseline (non-stress) concentrations of each hormone were comparable among the groups. As compared to saline controls, ACTH concentrations were significantly higher during stress at 30 and 60 minutes in the high-dose nicotine (HN) animals, with the average ACTH concentration during stress also being significantly higher in the HN rats. Neither nicotine regimen affected the corticosterone response to stress at any time-point. The prolactin response to stress was significantly reduced in the HN group at 45 and 60 minutes as compared to saline controls, with the average prolactin concentration also reduced during stress. During recovery, average ACTH concentrations were significantly higher in the HN group, and significantly lower in the LN group, with no differences found for either corticosterone or prolactin. The results indicate that exposure to a high-dose of nicotine during gestation, and to a very low-dose as well, produced functional alterations in adult male offspring as manifested by abnormal neuroendocrine responses to restraint stress. However, the differences between the nicotine and saline controls were sometimes as great as between the non-injected controls and the saline controls. Thus, any conclusions drawn about the long-term effects of prenatal nicotine on neuroendocrine responsivity to stress must be tempered by the influence of the repeated injection procedure.