Sex- and age-dependent differences in nicotine susceptibility evoked by developmental exposure to tobacco smoke and/or ethanol in mice

Abstract

Either tobacco smoking or alcohol consumption during pregnancy sex-selectively increases susceptibility to drugs of abuse later in life. Considering that pregnant smoking women are frequently intermittent consumers of alcoholic beverages, here, we investigated whether a short-term ethanol exposure restricted to the brain growth spurt period when combined with chronic developmental exposure to tobacco smoke aggravates susceptibility to nicotine in adolescent and adult mice. Swiss male and female mice were exposed to tobacco smoke (SMK; research cigarettes 3R4F, whole-body exposure, 8 h/daily) or ambient air during the gestational period and until the tenth postnatal day (PN). Ethanol (ETOH, 2 g/Kg, 25%, i.p.) or saline was injected in the pups every other day from PN2 to PN10. There were no significant differences in cotinine (nicotine metabolite) and ethanol serum levels among SMK, ETOH and SMK + ETOH groups. During adolescence (PN30) and adulthood (PN90), nicotine (NIC, 0.5 mg/Kg) susceptibility was evaluated in the conditioned place preference and open field tests. NIC impact was more evident in females: SMK, ETOH and SMK + ETOH adolescent females were equally more susceptible to nicotine-induced place preference than control animals. At adulthood, SMK and SMK + ETOH adult females exhibited a nicotine-evoked hyperlocomotor profile in the open field, with a stronger effect in the SMK + ETOH group. Our results indicate that ethanol exposure during the brain growth spurt, when combined to developmental exposure to tobacco smoke, increases nicotine susceptibility with stronger effects in adult females. This result represents a worsened outcome from the early developmental dual exposure and may predispose nicotine use/abuse later in life.

Lifetime caffeine and adolescent nicotine exposure in mice: effects on anxiety-like behavior and reward

“…81,82 Here, 0.5 mg/Kg of nicotine increased locomotor activity and time spent in the non-preferred chamber after conditioning during adolescence, which corroborates previous studies from our group. 59,60,83…”

“…81,82 Here, 0.5 mg/Kg of nicotine increased locomotor activity and time spent in the non-preferred chamber after conditioning during adolescence, which corroborates previous studies from our group. 59,60,83 Regarding the CPP, the increased time spent in the nonpreferred chamber indicates nicotine-evoked conditioning. However, the use of a biased CPP design makes it difficult to identify the participation of nicotine anxiolytic-like effects on its place preference conditioning, since a decrease in anxiety levels could increase the time spent in the nonpreferred chamber by reducing the aversion for this chamber.…”

“…The other chamber has walls painted with alternating white and black horizontal stripes and a checkered steel grid floor. The test protocol 59,60 consisted of four phases: habituation, pretest session, conditioning sessions, and test session. In the first 2 days (PN28-29), the animals received a once-daily i.p.…”