Nicotine Exposure during Adolescence Leads to Short- and Long-Term Changes in Spike Timing-Dependent Plasticity in Rat Prefrontal Cortex

Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 08/2012; 32(31):10484-93. DOI: 10.1523/JNEUROSCI.5502-11.2012
Source: PubMed


Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age can compromise the normal course of prefrontal development and lead to cognitive impairments in later life. Recently, we reported that nicotine exposure during adolescence results in a short-term increase and lasting reduction in synaptic mGluR2 levels in the rat mPFC, causing attention deficits during adulthood. It is unknown how changed synaptic mGluR2 levels after adolescent nicotine exposure affect the ability of mPFC synapses to undergo long-term synaptic plasticity. Here, we addressed this question. To model nicotine exposure, adolescent (P34-P43) or adult (P60-P69) rats were treated with nicotine injections three times per day for 10 d. We found that, both during acute activation of nicotinic receptors in the adolescent mPFC as well as immediately following nicotine treatment during adolescence, long-term plasticity in response to timed presynaptic and postsynaptic activity (tLTP) was strongly reduced. In contrast, in the mPFC of adult rats 5 weeks after they received nicotine treatment during adolescence, but not during adulthood, tLTP was increased. Short- and long-term adaptation of mPFC synaptic plasticity after adolescent nicotine exposure could be explained by changed mGluR2 signaling. Blocking mGluR2s augmented tLTP, whereas activating mGluR2s reduced tLTP. Our findings suggest neuronal mechanisms by which exposure to nicotine during adolescence alters the rules for spike timing-dependent plasticity in prefrontal networks that may explain the observed deficits in cognitive performance in later life.

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Available from: Natalia A Goriounova
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    • "In our case, nicotine exposure, occurring during adolescence, a still plastic developmental time window (see Introduction), resulted in persistent changes due to drug-induced organizational events on specific gene pathways. These findings raise the attention of an emerging literature that describes the lasting effects of adolescent nicotine exposure on cognitive and motivational systems in preclinical and clinical reports (Dao et al. 2011; Goriounova and Mansvelder 2012). A different mechanism of regulation should be hypothesized for the expression of the BDNF, since this gene shows similar basal expression in WT and HRM in prefrontal cortex and hippocampus, in agreement with published results (Ognibene et al. 2008, Romano et al. 2013). "
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    ABSTRACT: We have recently reported nicotine-induced stimulation of reelin and glutamic acid decarboxylase 67 (GAD67) mRNA expression levels in the brain of heterozygous reeler mice (HRM), a putative animal model for the study of symptoms relevant to major behavioral disorders. We aimed to evaluate long-term behavioral effects and brain molecular changes as a result of adaptations to nicotine exposure in the developing HRM males. Adolescent mice (pnd 37-42) were exposed to oral nicotine (10 mg/l) in a 6-day free-choice drinking schedule. As expected, no differences in total nicotine intake between WT (wild-type) mice and HRM were found. Long-term behavioral effects and brain molecular changes, as a consequence of nicotine exposure during adolescence, were only evidenced in HRM. Indeed, HRM perseverative exploratory behavior and poor cognitive performance were modulated to WT levels by subchronic exposure to nicotine during development. Furthermore, the expected reduction in the expression of mRNA of reelin and GAD67 in behaviorally relevant brain areas of HRM appeared persistently restored by nicotine. For brain-derived neurotrophic factor (BDNF) mRNA expression, no genotype-dependent changes appeared. However, expression levels were increased by previous nicotine in brains from both genotypes. The mRNA encoding for nicotine receptor subunits (α7, β2 and α4) did not differ between genotypes and as a result of previous nicotine exposure. These findings support the hypothesis of pre-existing vulnerability (based on haploinsufficiency of reelin) to brain and behavioral disorders and regulative short- and long-term effects associated with nicotine modulation.
    Full-text · Article · Dec 2013 · Psychopharmacology
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    • "However, when LTP was assessed following a 5-week withdrawal period (after P78), nicotine preexposed rats exhibited enhanced LTP compared to saline-treated controls. These short-and long-term adaptations, which were both linked to impairments in mGluR2 signaling in the mPFC, were not present in rats exposed to nicotine from P60 to P69 (Goriounova and Mansvelder, 2012). "
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    ABSTRACT: Adolescence is a period of significant neurobiological change that occurs as individuals transition from childhood to adulthood. Because the nervous system is in a relatively labile state during this stage of development, it may be especially sensitive to experience-induced plasticity. One such experience that is relatively common to adolescents is the exposure to drugs of abuse, particularly alcohol and psychostimulants. In this review, we highlight recent findings on the long-lasting effects of exposure to these drugs during adolescence in humans as well as in animal models. Whenever possible, our focus is on studies that use comparison groups of adolescent- and adult-exposed subjects as this is a more direct test of the hypothesis that adolescence represents a period of enhanced vulnerability to the effects of drug-induced plasticity. Lastly, we suggest areas of future investigation that are needed and methodological concerns that should be addressed.
    Full-text · Article · May 2013 · Neuroscience
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    • "Previously, we demonstrated that adolescent rats can re-establish nicotine-preference after 12 days of extinction using a single nicotine injection (Pascual et al. 2009). These results suggested that, if nicotine is administrated during adolescence, a preference could be maintained for long time; however, this was not the case when adult rats were used (Vastola et al. 2002;Belluzzi et al. 2004;Shram et al. 2006;Shearman et al. 2008).Furthermore, recent studies suggested that first experiences with drugs of abuse may have long-term impact on the development of drug-seeking behavior (Miller et al. 2001;Brielmaier et al. 2007;Goriounova and Mansvelder 2012). On the other hand, it has been demonstrated that individual sensitivity or vulnerability to the reinforcing effects of drugs of abuse is one of the most important factors underlying the development of drug consumption, where genetic, age, and other individual neurobiological differences could contribute to nicotine reward (Sabeti et al. 2002;Allen et al. 2007;Mandt et al. 2008). "
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    ABSTRACT: Rationale: Prior exposure to drugs of abuse may increase or decrease the reinforcing effects of the drug in later consumptions. Based on the initial locomotor activity (LA) response to an acute drug administration or to novelty in an open-field arena, animals can be classified as low or high LA responders (LR or HR). Few studies have used this classification with nicotine, and the results are controversial. Some authors suggested that nicotine can induce conditioned-place preference (CPP) following prior nicotine exposure, whereas others suggested that previous nicotine exposure extinguishes nicotine-CPP. Objective: To explore if the administration of nicotine in a novel environment without explicit behavioral consequences to classify animals in low and high nicotine responders (LNR and HNR) could affect the establishment of nicotine CPP in male Sprague-Dawley rats. Results: Prior exposure to a single dose of nicotine (0.4 mg/kg, subcutaneously) induced CPP in LNR rats after 14 days of conditioning (seven-trial) but not after two or eight conditioning days. In contrast, HNR rats did not show CPP under any condition. In addition, our results indicated that previous exposure to nicotine decreased its rewarding effects in eight conditioning days CPP (four-trial), which can be regularly established without prior exposure to nicotine. Conclusion: The results suggested that response to a single exposure to nicotine predicts the acquisition of nicotine preference in a 14-day conditioning protocol only for LNR rats. Thus, our findings demonstrated the relevance of using LNR and HNR classification when the individual susceptibility to nicotine preference is studied.
    Full-text · Article · Nov 2012 · Psychopharmacology
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