Combined exposure to nicotine and ethanol throughout full gestation results in enhanced acquisition of nicotine self-administration in young adult rat offspring

Abstract

Epidemiological evidence shows positive correlation between either maternal cigarette smoking or alcohol consumption on subsequent drug-taking behavior in offspring. However, the consequences of full gestational exposure to both drugs have not been studied experimentally despite concurrent use frequently reported among women of childbearing age. Such comorbid gestational drug exposure may increase susceptibility to acquiring cigarette smoking (i.e., nicotine self-administration), a major gateway drug. We developed a noninvasive rat model for exposure to both nicotine (2-6 mg kg(-1) day(-1)) and EtOH (4 g/kg gavage) that continued throughout pregnancy and postnatal (P) days 2-12, the rodent equivalent of the human third trimester, a critical brain developmental period. Offspring with this full gestational exposure to both drugs (Nic+EtOH) were compared to controls: nicotine alone, EtOH alone, pair-fed (comparable nutrition and handling), and ad libitum chow-fed. At P60-90, offspring had unlimited chronic access to acquire i.v. nicotine self-administration. There were no differences in gender ratio, stillbirths, birth weights, righting reflex, eye opening age, or weight gain. However, Nic+EtOH offspring of both genders acquired nicotine self-administration (15 or 30 microg kg(-1) injection(-1)) more rapidly, at a higher percentage, and at a higher level than offspring in the other cohorts. Full gestational Nic+EtOH exposure produced no overt alterations in standard postnatal measures but resulted in an enhanced acquisition of nicotine self-administration in young adult offspring.