Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long-Evans rats

Pharmacol Biochem Behav. 2002 Aug;73(1):131-40. doi: 10.1016/s0091-3057(02)00781-5.


Early neonatal environmental factors appear to have powerful and long-lasting influences on an organism's physiology and behavior. Long-Evans male rats separated from their dam for 3 h daily over the first 2 weeks of life (maternally separated, MS rats) when tested as adults exhibit exaggerated behavioral and neuroendocrine responses to stress compared to 15-min separated (handled, H) animals. The purpose of this study was to compare male and female adult rats that were MS, H or were undisturbed (nonhandled, NH) as neonates in anxiety-like behaviors, in the elevated plus-maze, and in response to startle-inducing auditory stimuli. We confirmed that MS males oversecrete corticosterone (CORT; 2.5-5 times) in response to mild handling stress. MS males and females were less likely to explore open arms of the plus-maze. MS males exhibited 35% higher startle amplitudes compared to controls. Furthermore, MS males were more likely to emit ultrasonic vocalizations in response to startle than were H controls. However, MS and control females did not differ in auditory startle response or in startle-induced ultrasonic vocalizations. Therefore, experiencing maternal separation results in a long-lasting increase in anxiety-like behaviors that occurs in a sex-dependent manner.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acoustic Stimulation / adverse effects
  • Animals
  • Animals, Newborn
  • Anxiety / blood*
  • Anxiety / psychology
  • Corticosterone / blood*
  • Female
  • Male
  • Maternal Deprivation*
  • Pregnancy
  • Rats
  • Rats, Long-Evans
  • Stress, Physiological / blood*
  • Stress, Physiological / psychology
  • Time
  • Vocalization, Animal / physiology


  • Corticosterone