Effects of nicotine exposure on locomotor activity and pCREB levels in the ventral striatum of adolescent rats

Laboratory of Neuropsychopharmacology, Department of Psychiatry and Neurosciences, University of South Florida College of Medicine, 3515 East Fletcher Avenue, Tampa, FL 33613, United States.
Behavioural brain research (Impact Factor: 3.03). 01/2012; 230(1):62-8. DOI: 10.1016/j.bbr.2012.01.036
Source: PubMed


Behavioral reactivity to novel stimuli, which is greater in the adolescent than young adult population, is associated with drug abuse liability, suggesting that the increased addiction vulnerability of adolescents may be related to heightened novel stimulus reactivity and underlying cellular processes. We examined the hypothesis that adolescent animals who exhibit higher novel stimulus reactivity, exhibit greater locomotor activity in response to nicotine than adolescents who exhibit lower novel stimulus reactivity, and that this difference is associated with alterations in CREB expression and activity in the ventral striatum (vStr) and prefrontal cortex (PFC). Adolescents exhibiting high locomotor activity (HLA) in the novel open field developed tolerance to the locomotor depressant effects of nicotine with fewer exposures and at lower doses than adolescents with low locomotor activity (LLA). Further, HLA adolescents exhibited lower CREB activity in the vStr than LLA adolescents and this difference was attenuated by repeated exposure to high, but not low doses of nicotine. Thus, inherent differences in the reactivity to novel stimulation during the adolescent period appear to predict sensitivity to the behavioral and cellular effects of nicotine and may underlie differences in progression to addiction.

8 Reads
  • Source
    • "Unfortunately, the findings here are also inconsistent. Philpot and colleagues found that adolescent HR rats developed sensitization to lower doses of nicotine than adolescent LR rats, though this was not the case at higher doses of nicotine (Philpot et al., 2012). Other sensitization work has been conducted in adolescent rats utilizing an intermittent nicotine sensitization regimen in which nicotine was administered every 3 days for a total of 4 injections (Aydin et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Not everyone who tries tobacco or other nicotine-containing products becomes a long-term user. Certain traits or factors that are differentially present in these individuals must be able to help health care providers and researchers determine who is more likely to become chronic users of nicotine-containing products. Some of these factors, particularly sensation-seeking/novelty, impulsivity, and anxiety, lend themselves to the creation of animal models of reactivity to nicotine. These models of reactivity to nicotine can improve the translational aspects of preclinical animal research on nicotine-induced behaviors and treatments in order to help reduce negative outcomes in human populations. The goal of this review is to evaluate the current status of animal models of individual differences that serve to predict the later behavioral effects of nicotine. The limited utility and inconsistency of existing novelty models is considered, as well as the promise of impulsivity and anxiety models in preclinical animal populations. Finally, other models that could be employed to extend the benefit of the current research are examined.
    Pharmacology Biochemistry and Behavior 09/2015; 138. DOI:10.1016/j.pbb.2015.09.017 · 2.78 Impact Factor
  • Source
    • "Although research on the effects of nicotine in fruit flies began fifty years ago, the work has mostly focused on nicotine resistance, as nicotine can be used as an insecticide [17]. In the past decade, it has been reported that fruit flies display rapid onset hyperactivity and spasmodic movement when exposed to volatilized nicotine; in addition, similar to mammals, dopaminergic signaling and the cAMP/CREB pathway play important roles in these effects [18], [19], [20], [21], indicating that some conserved mechanisms are shared between the fruit fly and mammals. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence.
    PLoS ONE 12/2012; 7(12):e52521. DOI:10.1371/journal.pone.0052521 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Drug addiction is a psychiatric disease state, wherein a drug is impulsively and compulsively self-administered despite negative consequences. This repeated administration results in permanent changes to nervous system physiology and architecture. The molecular pathways affected by addictive drugs are complex and inter-dependent on each other. Recently, various new proteins and protein families have been discovered to play a role in drug abuse. Emerging players in this phenomenon include TRP (Transient Receptor Potential) family channels, which are primarily known to function in sensory systems. Several TRP family channels identified in both vertebrates and invertebrates are involved in psychostimulant-induced plasticity, suggesting their involvement in drug dependence. This review summarizes various observations, both from studies in humans and other organisms, which support a role for these channels in the development of drug-related behaviors.
    Life sciences 07/2012; 92(8). DOI:10.1016/j.lfs.2012.07.008 · 2.70 Impact Factor
Show more