Effects of environmental enrichment on ERK1/2 phosphorylation in the rat prefrontal cortex following nicotine-induced sensitization or nicotine self-administration

Eur J Neurosci. 2015 Jan;41(1):109-19. doi: 10.1111/ejn.12758. Epub 2014 Oct 18.


Rats raised in an enriched condition (EC) exhibit alterations in the neurobiological and behavioral response to nicotine compared with rats reared in an impoverished condition (IC) or a standard condition (SC). The current study determined whether environmental enrichment differentially regulates extracellular signal-regulated kinase1/2 (ERK1/2) activity in the prefrontal cortex in rats following nicotine sensitization or nicotine self-administration. Under the saline control condition, EC rats displayed diminished baseline activity and greater sensitization to repeated administration of nicotine compared with IC and SC rats. After repeated saline injections, the basal levels of phosphorylated ERK1/2 (pERK1/2) were higher in EC compared with IC and SC rats, which was negatively correlated with their respective baseline activities. Repeated nicotine (0.35 mg/kg) injections induced pERK1/2 to similar levels in SC and IC rats; however, the induction of pERK1/2 in EC rats by nicotine was not significantly different from saline controls, owing to their high baseline. In the self-administration paradigm, EC rats self-administered less nicotine (0.03 mg/kg/infusion) relative to IC or SC rats on a fixed ratio-1 schedule of reinforcement. Accordingly, no differences in pERK1/2 were found between EC and IC rats self-administering saline, whereas nicotine self-administration resulted in an increase in pERK1/2 in IC rats but not in EC rats. Furthermore, the levels of pERK1/2 in EC and IC rats were positively correlated with their respective total number of nicotine infusions. Thus, these findings suggest that environmental enrichment alters the basal and nicotine-mediated pERK1/2, which may contribute to enrichment-induced behavioral alterations in response to nicotine.

Keywords: ERK; environmental enrichment; nicotine; prefrontal cortex; self-administration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Environment*
  • Housing, Animal
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Nicotine / administration & dosage*
  • Nicotinic Agonists / administration & dosage*
  • Phosphorylation / drug effects
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / enzymology
  • Random Allocation
  • Rats, Sprague-Dawley
  • Reinforcement Schedule
  • Self Administration


  • Nicotinic Agonists
  • Nicotine
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3