EXPOSURE TO THRESHOLD DOSES OF NICOTINE IN-UTERO .1. NEUROENDOCRINE RESPONSE TO RESTRAINT STRESS IN ADULT MALE OFFSPRING

Gravid female rats were injected subcutaneously with saline or nicotin e (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, 4 5 and 60 minutes) and after (30, 60, 90 and 120 minutes) one hour of r estraint stress were studied. Baseline (non-stress) concentrations of each hormone were comparable among the groups. As compared to saline c ontrols, ACTH concentrations were significantly higher during stress a t 30 and 60 minutes in the high-dose nicotine (HN) animals, with the a verage ACTH concentration during stress also being significantly highe r in the HN rats. Neither nicotine regimen affected the corticosterone response to stress at any time-point. The prolactin response to stres s was significantly reduced in the I-IN group at 45 and 60 minutes as compared to saline controls, with the average prolactin concentration also reduced during stress. During recovery, average ACTH concentratio ns were significantly higher in the HN group, and significantly lower in the LN group, with no differences found for either corticosterone o r prolactin. The results indicate that exposure to a high-dose of nico tine during gestation, and to a very low-dose as well, produced functi onal alterations in adult male offspring as manifested by abnormal neu roendocrine responses to restraint stress. However, the differences be tween the nicotine and saline controls were sometimes as great as betw een the non-injected controls and the saline controls. Thus, any concl usions drawn about the long-term effects of prenatal nicotine on neuro endocrine responsivity to stress must be tempered by the influence of the repeated injection procedure.