Prenatal and early postnatal nicotine exposure adversely affects autoresuscitation in serotonin deficient rats

We investigated the effects of prenatal and early postnatal nicotine exposure in rat neonates treated with control vs. tryptophan deficient diets, the latter known to induce a brainstem 5‐HT deficiency. In P10 neonates, nicotine exposurefrom E4 to P10 at 6mg kg ‐1 day ‐1 exacerbates autoresuscitation failure in 5‐HT deficient rats (p<0.05) to a greater extent than in controls. Exposure to nicotine compounds the effects of 5‐HT deficiency whereas neither 5‐HT deficiency nor nicotine alone appears to affect the ability to autoresuscitate significantly. Furthermore, the recovery of eupnea and heart rate to baseline values following an anoxic event (which elicits an apnea accompanied by a bradycardia) is significantly delayed in 5‐HT deficient rats treated with nicotine, making them more susceptible to failure of autoresuscitation (p<0.05). In younger (P5) and older (P12 – 13) pups, neither 5‐HT deficiency nor nicotine exposure alone affects the ability to autoresuscitate; interestingly, the two factors combined also did not exacerbate autoresuscitation failure as seen in P10 pups. Our interpretation is that a critical developmental period, in combination with an existing underlying vulnerability (i.e. 5‐HT deficiency) and an exogenous stressor (i.e. nicotine), influences the likelihood of recovering from an anoxic event. Research is supported by the NIH Program Project Grant HD036379 (NICHD, PI, Dymecki, S. M.; Project PI, Nattie, E. E.). The authors would also like to acknowledge the generous support of the Tenney Fund (awarded to S. Lee).