Behavioral Teratogenicity Induced by Nonforced Maternal Nicotine Consumption

Abstract

Prenatal nicotine exposure (PNE) has been associated with increased prevalence of attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD) and substance abuse in exposed children and adolescents. Whether these syndromes are caused by nicotine exposure, or genetic and psychosocial adversities associated with maternal smoking is not completely clear. Animal models suggest a direct impact of PNE. However, the fact that nicotine is forcefully administrated in these paradigms raises some questions about the specificity of these findings. Pregnant C57BI/6J mice were allowed to choose drinking saccharin/nicotine solutions or pure water. Controls could choose saccharin solutions or pure water. Offspring were tested in spontaneous locomotion, fear-associated learning (trace conditioning), addictive (conditioned place preference), and depression-like (learned helplessness) behaviors. There was no significant difference in weight or pup number between the prenatal treatment groups. A significant effect of PNE was observed on spontaneous locomotion, preference for a cocaine-associated place, and latency to escape in the learned helplessness paradigm. Surprisingly, PNE mice exhibited an increased learning of trace-conditioned fear-associated cues. The hyperlocomotive behavior reported in animal models of PNE is not likely an artifact of forceful nicotine administration. The increased prevalence of ADHD, MDD and substance abuse observed in PNE children and adolescents is probably caused by direct behavioral teratogenic effects of PNE. The role of PNE as a risk factor of syndromes associated to increased learning of fear-associated cues such as post-traumatic stress disorder (PTSD) warrants further evaluation.

Prenatal Nicotine Exposure Impairs Executive Control Signals in Medial Prefrontal Cortex

“…In addition, experiments that have administered nicotine via drinking water at doses comparable to ours have found plasma nicotine levels between 21 and 60 ng/ml (Paz et al, 2007;Schneider et al, 2010). Our mothers consumed an average of 5.93 mg/kg/day of nicotine during pregnancy, which is within the range shown to produce behavioral deficits in offspring without causing physical impairments (Paz et al, 2007;Schneider et al, 2010). Nicotine-exposed mothers in the present experiment consumed significantly less water than controls during pregnancy (98.89 ml/kg/day; 131 ml/kg/day; t-test; Po0.01) and gained weight at a slower rate prior to pregnancy (0.21% gain per day; 0.68% gain per day; t-test; Po0.01), characteristics that have been observed before by Schneider et al (2010).…”

“…The range of nicotine between 1 and 6 mg/ kg/day has been shown to produce plasma nicotine levels in the range of 10-50 ng/ml in habitual smokers (Benowitz and Jacob, 1987). In addition, experiments that have administered nicotine via drinking water at doses comparable to ours have found plasma nicotine levels between 21 and 60 ng/ml (Paz et al, 2007;Schneider et al, 2010). Our mothers consumed an average of 5.93 mg/kg/day of nicotine during pregnancy, which is within the range shown to produce behavioral deficits in offspring without causing physical impairments (Paz et al, 2007;Schneider et al, 2010).…”

Nicotine and brain development

“…Furthermore, such females exhibit greater locomotor sensitization in response to cocaine challenge after a period of drug withdrawal (Franke et al, 2007). Prenatal nicotine exposure has also been shown to increase cocaine reward in both male and female mice (Paz et al, 2007), and to increase total cocaine intake in self-administration tests in male rats (Franke et al, in press). As well as alterations in response to abused drugs, prenatally exposed animals also show decreased initial drive to obtain a natural food reward, sucrose (Franke et al, in press).…”

Teratogenicity and Teratogenic Factors

“…Whether these syndromes are caused by nicotine (smoke) exposure itself or by genetic and psychosocial mechanisms is still not completely elucidated. 54 Studies have provided a correlation of teratogenic effects of alcohol and tobacco, and the risk of anorectal atresia. Animal researches have suggested that caffeine may potentiate the teratogenicity of these agents.…”