Limits...
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) active lever responses for the PS and PN groups are presented for the METH doses 0.0005, 0.0025, 0.005, 0.025, 0.05, and 0.1 mg/kg/injection according to a log10 scale. Data from the training dose, 0.05 mg/kg/injection, is shown on the graph as a point of reference, but was not included in the ANOVA. This point represents the average responding for 0.05 mg/kg/infusion METH from the day before testing with the 0.0005- to 0.1-mg/kg/infusion doses. PN animals showed a leftward shift of the dose-response curve relative to the PS rats [Prenatal Treatment × Dose interaction; F(1, 34) = 4.9, p < 0.05].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3376423&req=5

Figure 2: Mean (±SEM) active lever responses for the PS and PN groups are presented for the METH doses 0.0005, 0.0025, 0.005, 0.025, 0.05, and 0.1 mg/kg/injection according to a log10 scale. Data from the training dose, 0.05 mg/kg/injection, is shown on the graph as a point of reference, but was not included in the ANOVA. This point represents the average responding for 0.05 mg/kg/infusion METH from the day before testing with the 0.0005- to 0.1-mg/kg/infusion doses. PN animals showed a leftward shift of the dose-response curve relative to the PS rats [Prenatal Treatment × Dose interaction; F(1, 34) = 4.9, p < 0.05].

Mentions: A 2 × 2 × 5 mixed-factorial ANOVA revealed main effects of Dose [F(1, 34) = 43.6, p < 0.001] and Prenatal Treatment [F(1, 34) = 4.3, p < 0.05], and a significant Dose × Prenatal Treatment interaction [F(1, 34) = 4.9, p < 0.05]. Sex was not a significant factor in the analyses. The METH self-administration data are presented as two separate dose-response curves in Figure 2. As can be seen in Figure 2, varying the unit dose of IV METH produced the standard “U” shaped curve for the PN and PS groups, which is commonly observed when animals self-administer psychostimulant drugs, such as amphetamines or cocaine (Yokel, 1987). Furthermore, the PS and PN groups exhibited similar means of active lever presses when allowed to respond for the lowest and highest unit doses of IV METH tested. However, PS rats clearly showed peak responding at the 0.025-mg/kg/infusion dose, whereas the PN animals exhibited peak responding between the 0.005- and 0.025-mg/kg/infusion doses. The main effect of Prenatal Treatment indicates that PN animals responded more for METH compared to the PS rats. The significant Dose × Prenatal Treatment interaction indicates that the PN dose-response curve shifted to the left. Analysis of inactive lever responding revealed a significant effect of Dose [F(1, 34) = 26.9, p < 0.001] and no other significant effects were found. The means (±SEM) for inactive lever responding were 10.0 (±1.6), 8.9 (±1.3), 6.5 (±0.9), 5.0 (±0.8), and 3.9 (±0.6; data not shown) for the 0.0005, 0.0025, 0.005, 0.025, and 1.0 doses, respectively. The main effect of dose shows that rats responded more on the inactive lever when the dose was 0.0005 and responding on this lever decreased as the unit dose of METH increased.


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) active lever responses for the PS and PN groups are presented for the METH doses 0.0005, 0.0025, 0.005, 0.025, 0.05, and 0.1 mg/kg/injection according to a log10 scale. Data from the training dose, 0.05 mg/kg/injection, is shown on the graph as a point of reference, but was not included in the ANOVA. This point represents the average responding for 0.05 mg/kg/infusion METH from the day before testing with the 0.0005- to 0.1-mg/kg/infusion doses. PN animals showed a leftward shift of the dose-response curve relative to the PS rats [Prenatal Treatment × Dose interaction; F(1, 34) = 4.9, p < 0.05].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Mean (±SEM) active lever responses for the PS and PN groups are presented for the METH doses 0.0005, 0.0025, 0.005, 0.025, 0.05, and 0.1 mg/kg/injection according to a log10 scale. Data from the training dose, 0.05 mg/kg/injection, is shown on the graph as a point of reference, but was not included in the ANOVA. This point represents the average responding for 0.05 mg/kg/infusion METH from the day before testing with the 0.0005- to 0.1-mg/kg/infusion doses. PN animals showed a leftward shift of the dose-response curve relative to the PS rats [Prenatal Treatment × Dose interaction; F(1, 34) = 4.9, p < 0.05].
Mentions: A 2 × 2 × 5 mixed-factorial ANOVA revealed main effects of Dose [F(1, 34) = 43.6, p < 0.001] and Prenatal Treatment [F(1, 34) = 4.3, p < 0.05], and a significant Dose × Prenatal Treatment interaction [F(1, 34) = 4.9, p < 0.05]. Sex was not a significant factor in the analyses. The METH self-administration data are presented as two separate dose-response curves in Figure 2. As can be seen in Figure 2, varying the unit dose of IV METH produced the standard “U” shaped curve for the PN and PS groups, which is commonly observed when animals self-administer psychostimulant drugs, such as amphetamines or cocaine (Yokel, 1987). Furthermore, the PS and PN groups exhibited similar means of active lever presses when allowed to respond for the lowest and highest unit doses of IV METH tested. However, PS rats clearly showed peak responding at the 0.025-mg/kg/infusion dose, whereas the PN animals exhibited peak responding between the 0.005- and 0.025-mg/kg/infusion doses. The main effect of Prenatal Treatment indicates that PN animals responded more for METH compared to the PS rats. The significant Dose × Prenatal Treatment interaction indicates that the PN dose-response curve shifted to the left. Analysis of inactive lever responding revealed a significant effect of Dose [F(1, 34) = 26.9, p < 0.001] and no other significant effects were found. The means (±SEM) for inactive lever responding were 10.0 (±1.6), 8.9 (±1.3), 6.5 (±0.9), 5.0 (±0.8), and 3.9 (±0.6; data not shown) for the 0.0005, 0.0025, 0.005, 0.025, and 1.0 doses, respectively. The main effect of dose shows that rats responded more on the inactive lever when the dose was 0.0005 and responding on this lever decreased as the unit dose of METH increased.

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