Nicotine exposure during adolescence leads to short- and long-term changes in spike timing-dependent plasticity in rat prefrontal cortex

J Neurosci. 2012 Aug 1;32(31):10484-93. doi: 10.1523/JNEUROSCI.5502-11.2012.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Age Factors
  • Aging / physiology
  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Amino Acids / pharmacology
  • Animals
  • Animals, Newborn
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Electric Stimulation
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Female
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects*
  • Male
  • Neurons / drug effects*
  • Neurons / physiology
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Prefrontal Cortex / cytology*
  • Prefrontal Cortex / drug effects
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Time Factors

Substances

  • Amino Acids
  • Bridged Bicyclo Compounds, Heterocyclic
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • LY 379268
  • Nicotinic Agonists
  • alpha-methyl-4-phosphonophenylglycine
  • Nicotine
  • Alanine