Increased CRF-like and NPY-like immunoreactivity in adult rats exposed to nicotine during adolescence: relation to anxiety-like and depressive-like behavior

Neuropeptides. 2005 Aug;39(4):369-77. doi: 10.1016/j.npep.2005.06.002.


Objective: Recently, animal models have been developed that demonstrate that adolescent nicotine exposure produces neurobehavioral changes which persist into adulthood. This study further examined the impact of adolescent nicotine exposure on anxiety-like and depressive-like behavior, as well as on levels of corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) in this model.

Methods: Male adolescent rats (35-40 days old) were administered nicotine using Nicoderm CQ patches (Smith-Kline Beecham). Behavior in the elevated plus maze (EPM) and forced swim test (FST) was assessed 2-3 weeks after exposure ended. Brain levels of CRF and NPY were then assessed 5-6 weeks after behavioral tests were completed. In addition, blood and brain levels of nicotine resulting from nicotine treatment were examined.

Results: After 5 days of exposure to 5 mg/kg/day nicotine, blood levels of nicotine averaged 66+/-5 ng/ml and brain nicotine levels averaged 52+/-4 ng/g. Rats exposed to nicotine displayed an anxiety-like profile in the EPM (i.e., decreased time spent in the open arms) and an antidepressant-like profile in the FST (i.e., less time spent immobile). Rats exposed to nicotine also had increased hypothalamic and frontal cortical CRF, increased hypothalamic and hippocampal NPY, and a decreased ratio of NPY to CRF in the amygdala.

Conclusions: This study demonstrates that adolescent nicotine exposure produces lasting increases in anxiety-like behavior and may reduce depressive-like behavior. These behavioral changes also occurred in concert with alterations in CRF and NPY systems. Thus, lasting neurobehavioral changes associated with adolescent nicotine exposure may be related to allostatic changes in stress peptide systems.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Antibodies
  • Anxiety / metabolism*
  • Corticotropin-Releasing Hormone / immunology
  • Corticotropin-Releasing Hormone / metabolism*
  • Depression / metabolism*
  • Immunohistochemistry
  • Male
  • Maze Learning
  • Neuropeptide Y / immunology
  • Neuropeptide Y / metabolism*
  • Neurosecretory Systems / drug effects
  • Neurosecretory Systems / growth & development
  • Neurosecretory Systems / metabolism
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Swimming


  • Antibodies
  • Neuropeptide Y
  • Nicotinic Agonists
  • Nicotine
  • Corticotropin-Releasing Hormone