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Offspring of Prenatal IV Nicotine Exposure Exhibit Increased Sensitivity to the Reinforcing Effects of Methamphetamine.

Harrod SB, Lacy RT, Morgan AJ - Front Pharmacol (2012)

Bottom Line: Maternal smoking during pregnancy is associated with increased substance abuse in offspring.There were no sex differences in either experiment.These results indicate that IV PN-exposed adult offspring exhibited increased sensitivity to IV METH.

View Article: PubMed Central - PubMed

Affiliation: Behavioral Neuroscience Program, Department of Psychology, University of South Carolina Columbia, SC, USA.

ABSTRACT
Maternal smoking during pregnancy is associated with increased substance abuse in offspring. Preclinical research shows that in utero exposure to nicotine, the primary psychoactive compound in tobacco smoke, influences the neurodevelopment of reward systems and alters motivated behavior in offspring. The present study determined if prenatal nicotine (PN) exposure altered the sensitivity to the reinforcing and aversive effects of methamphetamine (METH) in offspring using a low dose, intravenous (IV) exposure method. Pregnant dams were administered nicotine (0.05 mg/kg/injection) or prenatal saline (PS) 3×/day on gestational days 8-21, and adult offspring were tested using METH self-administration (experiment 1) or METH-induced conditioned taste aversion (CTA; experiment 2) procedures. For METH self-administration, animals were trained to respond for IV METH (0.05 mg/kg/infusion; fixed-ratio 3) and they were tested on varying doses of the reinforcer (0.0005-1.0 mg/kg/infusion). For METH CTA, rats received three saccharin and METH pairings (0, 0.3, or 0.5 mg/kg, sc) followed by 14 daily extinction trials. Experiment 1: PN and PS animals exhibited inverted U-shaped dose-response curves; however, the PN animal's curve was shifted to the left, suggesting PN animals were more sensitive to the reinforcing effects of METH. Experiment 2: METH CTA was acquired in a dose-dependent manner and the factor of PN exposure was not related to the acquisition or extinction of METH-induced CTA. There were no sex differences in either experiment. These results indicate that IV PN-exposed adult offspring exhibited increased sensitivity to IV METH. This suggests that PN exposure, via maternal smoking, will alter the reinforcing effects of METH during later stages of development, and furthermore, will influence substance use vulnerability in adult human offspring.

No MeSH data available.


Related in: MedlinePlus

Mean (±SEM) percent of control saccharin consumption (ml/g) data from the acquisition phase of the experiment. The CS was saccharin (0.1%, w/v) and the US was METH (SAL, 0.3 or 0.56 mg/kg). Data are shown as percent of control for the PS and PN animals treated with METH across conditioning days 1–3. There were no significant effects or interactions with the factor of Prenatal Treatment or Sex.
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Figure 3: Mean (±SEM) percent of control saccharin consumption (ml/g) data from the acquisition phase of the experiment. The CS was saccharin (0.1%, w/v) and the US was METH (SAL, 0.3 or 0.56 mg/kg). Data are shown as percent of control for the PS and PN animals treated with METH across conditioning days 1–3. There were no significant effects or interactions with the factor of Prenatal Treatment or Sex.

Mentions: A Sex × Prenatal Treatment × Dose × Day (2 × 2 × 3 × 3) mixed-factorial ANOVA was conducted on the weight-corrected data. The analysis revealed a main effect of Sex: [F(1, 224) = 114.9, p < 0.001], which indicates that females consumed more saccharin relative to males. According to this analysis females consumed an average of 0.06 ml/g of saccharin (SEM = 0.001), whereas males consumed an average of 0.04 ml/g of saccharin (SEM = 0.001; data not shown). Percent of control values were calculated, and a Sex × Prenatal Treatment × Dose × Day (2 × 2 × 2 × 3) mixed-factorial ANOVA was conducted on these data in order to adequately assess potential sex differences in CTA. The analysis revealed no significant effects of Sex or Prenatal Treatment. Figure 3 shows the acquisition curves (% of control) for PN and PS groups injected with METH 0.3 or 0.56 mg/kg by conditioning trials. The PN and PS groups represent both males and females; however, the factors of Prenatal Treatment are represented on Figure 3 because prenatal treatment was the focus of the experiment. The significant main effect of Day shows that animals treated with the METH US exhibited decreased saccharin consumption as a function of conditioning day [F(2, 152) = 484.8, p < 0.001] and the main effect of Dose indicates that overall the magnitude of CTA was greater in the METH 0.56 mg/kg group [means (±SEM) = 0.667 (±0.018)], relative to the METH 0.3 mg/kg group [0.798 (±0.018); F(1, 76) = 26.9, p < 0.001]. Moreover, repeated saccharin-METH pairings produced a progressive increase in the magnitude of CTA, and greater avoidance behavior was observed from animals injected with the higher dose of METH, according to the significant Day × Dose interaction [F(2, 152) = 20.5, p < 0.001].


Offspring of Prenatal IV Nicotine Exposure Exhibit Increased Sensitivity to the Reinforcing Effects of Methamphetamine.

Harrod SB, Lacy RT, Morgan AJ - Front Pharmacol (2012)

Mean (±SEM) percent of control saccharin consumption (ml/g) data from the acquisition phase of the experiment. The CS was saccharin (0.1%, w/v) and the US was METH (SAL, 0.3 or 0.56 mg/kg). Data are shown as percent of control for the PS and PN animals treated with METH across conditioning days 1–3. There were no significant effects or interactions with the factor of Prenatal Treatment or Sex.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376423&req=5

Figure 3: Mean (±SEM) percent of control saccharin consumption (ml/g) data from the acquisition phase of the experiment. The CS was saccharin (0.1%, w/v) and the US was METH (SAL, 0.3 or 0.56 mg/kg). Data are shown as percent of control for the PS and PN animals treated with METH across conditioning days 1–3. There were no significant effects or interactions with the factor of Prenatal Treatment or Sex.
Mentions: A Sex × Prenatal Treatment × Dose × Day (2 × 2 × 3 × 3) mixed-factorial ANOVA was conducted on the weight-corrected data. The analysis revealed a main effect of Sex: [F(1, 224) = 114.9, p < 0.001], which indicates that females consumed more saccharin relative to males. According to this analysis females consumed an average of 0.06 ml/g of saccharin (SEM = 0.001), whereas males consumed an average of 0.04 ml/g of saccharin (SEM = 0.001; data not shown). Percent of control values were calculated, and a Sex × Prenatal Treatment × Dose × Day (2 × 2 × 2 × 3) mixed-factorial ANOVA was conducted on these data in order to adequately assess potential sex differences in CTA. The analysis revealed no significant effects of Sex or Prenatal Treatment. Figure 3 shows the acquisition curves (% of control) for PN and PS groups injected with METH 0.3 or 0.56 mg/kg by conditioning trials. The PN and PS groups represent both males and females; however, the factors of Prenatal Treatment are represented on Figure 3 because prenatal treatment was the focus of the experiment. The significant main effect of Day shows that animals treated with the METH US exhibited decreased saccharin consumption as a function of conditioning day [F(2, 152) = 484.8, p < 0.001] and the main effect of Dose indicates that overall the magnitude of CTA was greater in the METH 0.56 mg/kg group [means (±SEM) = 0.667 (±0.018)], relative to the METH 0.3 mg/kg group [0.798 (±0.018); F(1, 76) = 26.9, p < 0.001]. Moreover, repeated saccharin-METH pairings produced a progressive increase in the magnitude of CTA, and greater avoidance behavior was observed from animals injected with the higher dose of METH, according to the significant Day × Dose interaction [F(2, 152) = 20.5, p < 0.001].

Bottom Line: Maternal smoking during pregnancy is associated with increased substance abuse in offspring.There were no sex differences in either experiment.These results indicate that IV PN-exposed adult offspring exhibited increased sensitivity to IV METH.

View Article: PubMed Central - PubMed

Affiliation: Behavioral Neuroscience Program, Department of Psychology, University of South Carolina Columbia, SC, USA.

ABSTRACT
Maternal smoking during pregnancy is associated with increased substance abuse in offspring. Preclinical research shows that in utero exposure to nicotine, the primary psychoactive compound in tobacco smoke, influences the neurodevelopment of reward systems and alters motivated behavior in offspring. The present study determined if prenatal nicotine (PN) exposure altered the sensitivity to the reinforcing and aversive effects of methamphetamine (METH) in offspring using a low dose, intravenous (IV) exposure method. Pregnant dams were administered nicotine (0.05 mg/kg/injection) or prenatal saline (PS) 3×/day on gestational days 8-21, and adult offspring were tested using METH self-administration (experiment 1) or METH-induced conditioned taste aversion (CTA; experiment 2) procedures. For METH self-administration, animals were trained to respond for IV METH (0.05 mg/kg/infusion; fixed-ratio 3) and they were tested on varying doses of the reinforcer (0.0005-1.0 mg/kg/infusion). For METH CTA, rats received three saccharin and METH pairings (0, 0.3, or 0.5 mg/kg, sc) followed by 14 daily extinction trials. Experiment 1: PN and PS animals exhibited inverted U-shaped dose-response curves; however, the PN animal's curve was shifted to the left, suggesting PN animals were more sensitive to the reinforcing effects of METH. Experiment 2: METH CTA was acquired in a dose-dependent manner and the factor of PN exposure was not related to the acquisition or extinction of METH-induced CTA. There were no sex differences in either experiment. These results indicate that IV PN-exposed adult offspring exhibited increased sensitivity to IV METH. This suggests that PN exposure, via maternal smoking, will alter the reinforcing effects of METH during later stages of development, and furthermore, will influence substance use vulnerability in adult human offspring.

No MeSH data available.


Related in: MedlinePlus