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Nicotine-Cadmium Interaction Alters Exploratory Motor Function and Increased Anxiety in Adult Male Mice.

ABSTRACT: In this study we evaluated the time dependence in cadmium-nicotine interaction and its effect on motor function, anxiety linked behavioural changes, serum electrolytes, and weight after acute and chronic treatment in adult male mice. Animals were separated randomly into four groups of n = 6 animals each. Treatment was done with nicotine, cadmium, or nicotine-cadmium for 21 days. A fourth group received normal saline for the same duration (control). Average weight was determined at 7-day interval for the acute (D1-D7) and chronic (D7-D21) treatment phases. Similarly, the behavioural tests for exploratory motor function (open field test) and anxiety were evaluated. Serum electrolytes were measured after the chronic phase. Nicotine, cadmium, and nicotine-cadmium treatments caused no significant change in body weight after the acute phase while cadmium-nicotine and cadmium caused a decline in weight after the chronic phase. This suggests the role of cadmium in the weight loss observed in tobacco smoke users. Both nicotine and cadmium raised serum Ca(2+) concentration and had no significant effect on K(+) ion when compared with the control. In addition, nicotine-cadmium treatment increased bioaccumulation of Cd(2+) in the serum which corresponded to a decrease in body weight, motor function, and an increase in anxiety.

SUBMITTER: Chris Ajonijebu D

PROVIDER: S-EPMC4437340 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Nicotine-Cadmium Interaction Alters Exploratory Motor Function and Increased Anxiety in Adult Male Mice.

Chris Ajonijebu Duyilemi D Adeyemi Adeniyi Philip P Oloruntoba Adekeye Adeshina A Peter Olatunji Babawale B Olakunle Ishola Azeez A Michael Ogundele Olalekan O

Journal of neurodegenerative diseases 20141112

In this study we evaluated the time dependence in cadmium-nicotine interaction and its effect on motor function, anxiety linked behavioural changes, serum electrolytes, and weight after acute and chronic treatment in adult male mice. Animals were separated randomly into four groups of n = 6 animals each. Treatment was done with nicotine, cadmium, or nicotine-cadmium for 21 days. A fourth group received normal saline for the same duration (control). Average weight was determined at 7-day interval ...[more]

PMID: 26317007

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Project description:Neurodevelopment is a tightly coordinated process, in which genome is exposed to spectra of endogenous agents at different stages of differentiation. Increasing body of evidence suggests that DNA damage is an important feature of developing brain, tightly linked to gene expression programs and neuronal activity. Some of the most frequent DNA damage includes changes to DNA bases, recognized by DNA glycosylases and repaired through base excision repair (BER). The only mammalian DNA glycosylase able to remove frequent alkylated DNA based is alkyladenine DNA glycosylase (Aag, aka Mpg). Recently we showed that, besides participation in DNA repair, AAG affects expression of neurodevelopmental genes in human cells. Aag was further proposed to act as reader of epigenetic marks, including 5-hydroxymethylcytosine (5hmC), in the mouse brain. Despite the evidence of potential Aag involvement in the key brain processes, the impact of Aag loss on developing brain remains unknown. Here, by using Aag knockout (Aag-/-) mice, we show that Aag absence leads to reduced DNA damage levels, evident in lowered number of γH2AX foci in P5 hippocampi. This is accompanied by changes in 5hmC signal intensity in different hippocampal regions. Analysis of gene expression in hippocampus and prefrontal cortex, at multiple developmental stages, indicates that lack of Aag results in altered gene expression, primarily of genes involved in regulation of response to stress. One of the most prominent genes deregulated in Aag-dependent manner, at all tested developmental stages, is aldehyde dehydrogenase 2 (Aldh2). In line with the changes in hippocampal DNA damage levels and the gene expression, adult Aag-/- mice exhibit altered behavior, evident in decreased anxiety in the Elevated Zero Maze and increased alternations in the Elevated T Maze tests. Taken together these results suggests that Aag has functions in modulation of genome dynamics during brain development, important for animal behavior.

Project description:IntroductionDuring adolescence, exposure to nicotine or cannabis independently induces effects on neuromaturation and later cognitive function. However, the potential effect of both drugs under co-use conditions has become of increasing concern given the prevalence of e-cigarettes, legalization of cannabis, and availability of synthetic "spice" cannabinoid agonists.Aims and methodsThe current studies investigated the effects of exposure to a cannabinoid receptor agonist (WIN55,212-2) and/or nicotine over a discrete time period in mid-adolescence on later intravenous nicotine self-administration in adult male and female mice. We further examined whether cannabinoid agonist administration in adulthood would alter nicotine reinforcement, with either acute or chronic pairing across 7 days.ResultsWe found that adult males exhibited increased nicotine self-administration at a lower, rewarding nicotine dose following adolescent cannabinoid exposure, either alone or with nicotine coadministration. In contrast, adult females demonstrated an opposing effect in which adolescent cannabinoid and nicotine coexposure resulted in decreased nicotine intake compared with the nicotine only and control groups. Furthermore, after maintaining nicotine self-administration across sessions, pretreatment with a low dose of the cannabinoid agonist decreased nicotine intake in both male and female control mice, and this lowering effect was evidenced after both acute and chronic treatment. However, the cannabinoid agonist was ineffective in altering nicotine intake in mice previously exposed to nicotine, cannabinoid agonist, or both during adolescence.ConclusionsThese data provide evidence that adolescent drug exposure can alter later nicotine reinforcement in a sex-specific manner and can further modulate the effectiveness of interventions in reducing nicotine intake during adulthood.ImplicationsThese studies demonstrate a significant impact of nicotine, cannabinoids, or coexposure on developmental processes during adolescence. Differential effects were observed within each sex, with opposing results found for cannabinoid exposure on nicotine intake in males and females. Intriguingly, we also evidenced resistance to the lowering effects of a cannabinoid agonist on nicotine intake in adulthood based on adolescent drug exposure. Thus, these findings have important implications for our understanding of the impact of nicotine and cannabinoids (eg, Δ9-tetrahydrocannabinol (THC) and synthetic "spice" cannabinoids) during development, with further implications for the effectiveness of therapeutic interventions based on prior drug exposure in youth.

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Project description:Anxiety disorders and nicotine use are significant contributors to global morbidity and mortality as independent and comorbid diseases. Early-life stress, potentially via stress-induced hypothalamic-pituitary-adrenal axis (HPA) dysregulation, can exacerbate both. However, little is known about the factors that predispose individuals to the development of both anxiety disorders and nicotine use. Here, we examined the relationship between anxiety-like behaviors and nicotine responses following adolescent stress. Adolescent male and female BALB/cJ mice were exposed to either chronic variable social stress (CVSS) or control conditions. CVSS consisted of repeated cycles of social isolation and social reorganization. In adulthood, anxiety-like behavior and social avoidance were measured using the elevated plus-maze (EPM) and social approach-avoidance test, respectively. Nicotine responses were assessed with acute effects on body temperature, corticosterone production, locomotor activity, and voluntary oral nicotine consumption. Adolescent stress had sex-dependent effects on nicotine responses and exploratory behavior, but did not affect anxiety-like behavior or social avoidance in males or females. Adult CVSS males exhibited less exploratory behavior, as indicated by reduced exploratory locomotion in the EPM and social approach-avoidance test, compared to controls. Adolescent stress did not affect nicotine-induced hypothermia in either sex, but CVSS males exhibited augmented nicotine-induced locomotion during late adolescence and voluntarily consumed less nicotine during adulthood. Stress effects on male nicotine-induced locomotion were associated with individual differences in exploratory locomotion in the EPM and social approach-avoidance test. Relative to controls, adult CVSS males and females also exhibited reduced corticosterone levels at baseline and adult male CVSS mice exhibited increased corticosterone levels following an acute nicotine injection. Results suggest that the altered nicotine responses observed in CVSS males may be associated with HPA dysregulation. Taken together, adolescent social stress influences later-life nicotine responses and exploratory behavior. However, there is little evidence of an association between nicotine responses and prototypical anxiety-like behavior or social avoidance in BALB/cJ mice.

Dataset Information

Nicotine-Cadmium Interaction Alters Exploratory Motor Function and Increased Anxiety in Adult Male Mice.

Publications

Nicotine-Cadmium Interaction Alters Exploratory Motor Function and Increased Anxiety in Adult Male Mice.

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