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.
"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 . 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 , , , , 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 abstract][Hide abstract] ABSTRACT: This study determined the effects of adolescent nicotine administration on adult alcohol preference in rats exhibiting high or low behavioral reactivity to a novel environment, and ascertained whether nicotine altered ΔFosB in the ventral striatum (vStr) and prefrontal cortex (PFC) immediately after drug administration or after rats matured to adulthood. Animals were characterized as exhibiting high (HLA) or low (LLA) locomotor activity in the novel open field on postnatal day (PND) 31 and received injections of saline (0.9%) or nicotine (0.56mg free base/kg) from PND 35-42. Ethanol-induced conditioned place preference (CPP) was assessed on PND 68 following 8 days conditioning in a biased paradigm; ΔFosB was measured on PND 43 or PND 68. Following adolescent nicotine exposure, HLA animals demonstrated a CPP when conditioned with ethanol; LLA animals were unaffected. Further, adolescent nicotine exposure for 8 days increased levels of ΔFosB in limbic regions in both HLA and LLA rats, but this increase persisted into adulthood only in LLA animals. Results indicate that adolescent nicotine exposure facilitates the establishment of an ethanol CPP in HLA rats, and that sustained elevations in ΔFosB are not necessary or sufficient for the establishment of an ethanol CPP in adulthood. These studies underscore the importance of assessing behavioral phenotype when determining the behavioral and cellular effects of adolescent nicotine exposure.
Behavioural brain research 01/2014; 262. DOI:10.1016/j.bbr.2013.12.014 · 3.03 Impact Factor
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