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. 2014 Mar:102:1-8.
doi: 10.1016/j.brainresbull.2014.01.004. Epub 2014 Jan 30.

Nicotine administration in adolescence reprograms the subsequent response to nicotine treatment and withdrawal in adulthood: sex-selective effects on cerebrocortical serotonergic function

Theodore A Slotkin  1 , Jennifer Card  2 , Frederic J Seidler  2
Affiliations

Nicotine administration in adolescence reprograms the subsequent response to nicotine treatment and withdrawal in adulthood: sex-selective effects on cerebrocortical serotonergic function

Theodore A Slotkin et al. Brain Res Bull. 2014 Mar.

Abstract

Nicotine exposure in adolescence produces lasting changes in subsequent behavioral responses to addictive agents. We gave nicotine to adolescent rats (postnatal days PN30-47), simulating plasma levels in smokers, and then examined the subsequent effects of nicotine given again in adulthood (PN90-107), focusing on cerebrocortical serotonin levels and utilization (turnover) as an index of presynaptic activity of circuits involved in emotional state. Our evaluations encompassed responses during the period of adult nicotine treatment (PN105) and withdrawal (PN110, PN120, PN130), as well as long-term changes (PN180). In males, prior exposure to nicotine in adolescence greatly augmented the increase in serotonin turnover evoked by nicotine given in adulthood, an interaction that was further exacerbated during withdrawal. The effect was sufficiently large that it led to significant depletion of serotonin stores, an effect that was not seen with nicotine given alone in either adolescence or adulthood. In females, adolescent nicotine exposure blunted or delayed the spike in serotonin turnover evoked by withdrawal from adult nicotine treatment, a totally different effect from the interaction seen in males. Combined with earlier work showing persistent dysregulation of serotonin receptor expression and receptor coupling, the present results indicate that adolescent nicotine exposure reprograms future responses of 5HT systems to nicotine, changes that may contribute to life-long vulnerability to relapse and re-addiction.

Keywords: Adolescence; Nicotine; Serotonin; Sex differences; Withdrawal.

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Conflict of interest statement

Conflict of interest statement: TAS has received consultant income in the past three years from the following firms: The Calwell Practice (Charleston WV), Finnegan Henderson Farabow Garrett & Dunner (Washington DC), Carter Law (Peoria IL), Gutglass Erickson Bonville & Larson (Madison WI), The Killino Firm (Philadelphia PA), Alexander Hawes (San Jose, CA), Pardieck Law (Seymour, IN), Tummel & Casso (Edinburg, TX), Shanahan Law Group (Raleigh NC), and Chaperone Therapeutics (Research Triangle Park, NC).

Figures

Figure 1
Figure 1
Schematic of nicotine treatment regimens and sampling times.
Figure 2
Figure 2
Effects of adolescent nicotine administration on 5HT concentrations (A) and turnover (B). Animals received vehicle or nicotine from PN30-47 and then were implanted in adulthood with minipumps delivering vehicle from PN90-107. Data represent means and standard errors. Multivariate ANOVA (factors of treatment, sex, age) indicated no significant effects of nicotine or interaction of nicotine with the other variables; accordingly, no lower-order tests were performed. These data then provided the basal values for comparisons of the effects of adult nicotine administration and withdrawal shown in Figure 3. Abbreviation: NS, not significant.
Figure 3
Figure 3
Effects of adult nicotine administration and withdrawal in animals with or without prior exposure to nicotine in adolescence: (A) 5HT concentrations, (B) 5HT turnover. Data represent means and standard errors, shown as the percent change from the corresponding basal values given in Figure 2. ANOVA at the top of each panel gives the result of multivariate comparisons incorporating all factors (adolescent treatment, sex, age). Because nicotine treatment interacted with sex, lower-order tests are shown separately for males and females. Where a nicotine × age interaction was detected in the lower-order test, asterisks show the individual ages where the response to adult nicotine administration differed significantly between the group given adolescent nicotine vs. adolescent vehicle. Abbreviation: NS, not significant.
See this image and copyright information in PMC

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