Increased nicotine self-administration following prenatal exposure in female rats

Abstract

There is a significant association between maternal cigarette smoking during pregnancy and greater subsequent risk of smoking in female offspring. In animal models, prenatal nicotine exposure causes persistent alterations in cholinergic and monoaminergic systems, both of which are important for nicotine actions underlying tobacco addiction. Accordingly, the current study was conducted to determine if there is a cause-and-effect relationship between prenatal nicotine exposure and nicotine self-administration starting in adolescence. Pregnant rats were administered nicotine (6 mg/kg/day) by osmotic minipump infusion throughout gestation and then, beginning in adolescence and continuing into adulthood, female offspring were given access to nicotine via a standard operant IV self-administration procedure (0.03 mg/kg/infusion). Gestational nicotine exposure did not alter the initial rate of nicotine self-administration. However, when animals underwent one week of forced abstinence and then had a second opportunity to self-administer nicotine, the prenatally-exposed animals showed a significantly greater rate of self-administration than did the controls. Prenatal nicotine exposure causes increased nicotine self-administration, which is revealed only when the animals are allowed to experience a period of nicotine abstinence. This supports a cause-and-effect relationship between the higher rates of smoking in the daughters of women who smoke cigarettes during pregnancy and implicates a role for nicotine in this effect. Our results further characterize the long-term liabilities of maternal smoking but also point to the potential liabilities of nicotine-based treatments for smoking cessation during pregnancy.

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

“…In fact, evidence exists that prenatal nicotine increases anxiety in rodents (Huang et al, 2007;Santiago and Huffman, 2013;Vaglenova et al, 2008), although also see Amos-Kroohs et al (2013). Exposed animals are more likely to self-administer nicotine later in life (Chistyakov et al, 2010;Levin et al, 2006). Others have shown that exposed rodents are more sensitive to the rewarding (Harrod et al, 2012) and locomotor-stimulating (Amos-Kroohs et al, 2013) properties of METH.…”

Nicotine and brain development

“…Although prenatally exposed females self-administer equivalent levels of nicotine to that of controls upon initial drug exposure, they ingest significantly more following a period of abstinence (Levin et al, 2006). Furthermore, such females exhibit greater locomotor sensitization in response to cocaine challenge after a period of drug withdrawal (Franke et al, 2007).…”

Estimating the Harms of Nicotine-Containing Products Using the MCDA Approach

“…Experience with these preparations suggests that their use is not associated with an increased risk of chronic obstructive pulmonary disease, lung cancer or cardiovascular disease [3,11] although there are reports that nicotine may be metabolized to compounds that are potentially carcinogenic [12,13] . Furthermore, studies with experimental animals suggest that the ingestion of nicotine during pregnancy can have adverse effects on the brain development of the fetus and the vulnerability of the progeny to nicotine dependence [14,15] . Relatively little direct information is available for the effects of maternal nicotine on human development and behaviour.…”