Sex and ovarian hormones influence vulnerability and motivation for nicotine during adolescence in rats - PubMed (original) (raw)

Sex and ovarian hormones influence vulnerability and motivation for nicotine during adolescence in rats

Wendy J Lynch. Pharmacol Biochem Behav. 2009 Nov.

Abstract

The purpose of this study was to examine sex differences in sensitivity to nicotine's reinforcing effects during adolescence, a hormone transition phase characterized by rapid and marked changes in levels of gonadal hormones. Male and female rats were trained to self-administer nicotine (5 or 10 microg/kg/infusion) under a fixed-ratio 1 schedule beginning on postnatal day 30. Following acquisition, responding was assessed under a progressive-ratio schedule until postnatal day 45 with blood sampling occurring prior to the first 5 sessions in order to determine the relationship between gonadal hormones (i.e., estradiol and progesterone in females and testosterone in males) and responding for nicotine. Under low dose conditions, a greater percentage of females than males acquired nicotine self-administration. Under progressive-ratio testing conditions, although adolescent females and males initially responded at similar levels, by the end of the adolescent testing period, females responded at higher levels than males to obtain nicotine infusions. Levels of responding under the progressive-ratio schedule were negatively associated with progesterone and positively associated with the ratio of estradiol to progesterone. These findings demonstrate an enhanced sensitivity in adolescent females as compared to adolescent males to nicotine's reinforcing effects with evidence implicating circulating hormone levels as modulating this sensitivity.

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Figures

Figure 1

Experimental timeline used to examine acquisition of nicotine self-administration (SA) under a fixed-ratio (FR) 1 schedule and subsequent maintenance self-administration under a progressive-ratio (PR) schedule. Progressive-ratio testing was assessed once rats acquired nicotine self-administration under the fixed-ratio schedule, with sessions beginning as early as postnatal day 32.

Figure 2

Data are presented as an inverse survival function to illustrate the percentage of female and male rats to meet the acquisition criterion by postnatal day 45 under the 5 and 10 µg/kg nicotine dose conditions. The asterisk indicates a significant sex difference (P<0.05). Insets show that number of inactive lever responses for male (open bars) and female (filled bars) rats for the 2 sessions that met the acquisition criterion. Each data point represents an N of 10 females and 12 males under the 5 µg/kg nicotine dose condition and an N of 15 females and 14 males under the 10 µg/kg nicotine dose condition.

Figure 3

The average number of responses on the active and inactive levers for the first five progressive-ratio sessions under the 5 and 10 µg/kg nicotine dose conditions. Each data point represents an N of 9 females and 6 males under the 5 µg/kg nicotine dose condition and an N of 14 females and 11 males under the 10 µg/kg nicotine dose condition.

Figure 4

(Top Panel) Data are plotted for each of the 12 females and 9 males for the relationship between serum hormones levels and the number of infusions obtained under the progressive-ratio schedule (E = estradiol; P = progesterone; T = testosterone). An asterisk indicates a significant difference from 0 (P<0.05). (Bottom Panels) Data are plotted for each of the 12 female rats for the relationship between serum concentration of progesterone (Left) and the ratio of estradiol to progesterone (Right) and the number of infusions obtained under the progressive-ratio schedule. Regression lines are also shown for each rat.

Figure 5

(Top Panels) The average number of active and inactive lever responses observed during the progressive-ratio nicotine self-administration sessions as function of postnatal day across the adolescent testing period under the 5 and 10 µg/kg nicotine dose conditions. The asterisk indicates a significant interaction of sex by time (P<0.05). Each data point represents an N of 7 females and 5 males under the 5 µg/kg nicotine dose condition and an N of 6 females and 8 males under the 10 µg/kg nicotine dose condition. Vertical bars with asterisks represents a significant effect of sex for last three sessions (P<0.05). (Bottom Panel) The average number of active and inactive lever responses observed under the progressive-ratio schedule as function of phase of the estrous cycle (Met/Die = metestrus/diestrus; Pro = proestrus; Est = estrus). The asterisk indicates a significant difference in the number of infusions obtained between estrus and the other 2 phases (P’s≤0.05). Each bar represents an N of 12.

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Sex and ovarian hormones influence vulnerability and motivation for nicotine during adolescence in rats - PubMed (original) (raw)