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.
    Psychopharmacology 12/2013; 231(8). DOI:10.1007/s00213-013-3388-y · 3.88 Impact Factor
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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.
    Neuroscience 05/2013; 249. DOI:10.1016/j.neuroscience.2013.05.026 · 3.36 Impact Factor
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    • "We found that the decrease in attention following adolescent nicotine exposure was (at least in part) caused by a decreased synaptic expression of the metabotropic glutamate receptor mGluR2 in the medial prefrontal cortex, because stimulation of this receptor by local infusion of an mGluR2/3 agonist relieved the attention deficits and brought the adolescent nicotine exposed animals back to the level of their control counterparts (Counotte et al., 2011a). This change in mGluR2 signaling in the mPFC in turn leads to an alteration of the rules for spike timing-dependent plasticity, meaning that the ability to filter information has decreased (Goriounova and Mansvelder, 2012). Thus, adolescent nicotine exposure affects synaptic signaling mechanisms involving metabotropic glutamate signaling in the mPFC. "
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    ABSTRACT: Nicotine has remarkably diverse effects on the brain. Being the main active compound in tobacco, nicotine can aversively affect brain development. However, it has the ability to act positively by restoring attentional capabilities in smokers. Here, we focus on nicotine exposure during the prenatal and adolescent developmental periods and specifically, we will review the long-lasting effects of nicotine on attention, both in humans and animal models. We discuss the reciprocal relation of the beneficial effects of nicotine, improving attention in smokers and in patients with neuropsychiatric diseases, such as schizophrenia and attention deficit/hyperactivity disorder, vs. nicotine-related attention deficits already caused during adolescence. Given the need for research on the mechanisms of nicotine's cognitive actions, we discuss some of the recent work performed in animals.
    Frontiers in Pharmacology 10/2012; 3:180. DOI:10.3389/fphar.2012.00180 · 3.80 Impact Factor
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