Effects of perinatal cocaine exposure on open field behavior and the response to corticotropin releasing hormone (CRH) in rat offspring

Thitinart Sithisarn, Henrietta S. Bada, Hongying Dai, David C. Randall, Sandra J. Legan

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Previous reports indicate that prenatal cocaine exposure alters specific behaviors and hypothalamic-pituitary-adrenal axis (HPA) function in the offspring. In most previous studies, cocaine was given via subcutaneous injections. However intravenous administration more closely mimics human cocaine abuse during pregnancy. Therefore, we investigated the effects of prenatal cocaine exposure via intravenous injection to the mothers on open field behavior and HPA axis function of the offspring. We hypothesized that prenatal cocaine exposure decreases immobility in a novel environment, and enhances the HPA response to stress. Dams received cocaine (COC) or vehicle (control, CON) intravenously from gestation day 8 to postnatal day (PD) 5. Behaviors were recorded in the open field on PD 28 (weanlings). As expected, perinatally cocaine-exposed offspring spent less time immobile and had a longer latency to entering the center zone. No other behavioral activities were different between the groups. On PD 43-50, adolescent male and female offspring received either corticotropin releasing hormone (CRH) or saline intravenously. Plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined before, and up to 60 min after injection. COC-exposed offspring of both sexes had higher basal CORT levels. Prenatal cocaine enhanced the CORT response to CRH/saline injections up to 60 min in males but not in females. These novel results show that perinatal administration of cocaine in a manner that most closely mimics human cocaine use has long-term effects on the offspring's behavioral response to stress and on HPA axis functions.

Original languageEnglish
Pages (from-to)136-144
Number of pages9
JournalBrain Research
StatePublished - Oct 25 2011

Bibliographical note

Funding Information:
We gratefully acknowledge the excellent technical assistance of Ms. Xiao-Li Peng. We also thank Mr. Timothy Crawford and Dr. Marta Mendiondo for their kind help with statistical analyses, and Dr. A. F. Parlow and the National Hormone and Peptide Program for ovine CRH. This study was partly funded by a Kentucky Children's Hospital Children's Miracle Network Grant awarded to S.J. L., H.S.B., D.C.R. and T.S., an endowment from the Mary Florence Jones Professorship awarded to H.S.B., and the support for T.S. by K30 HL04163 .


  • CRH
  • HPA axis
  • Neurobehavior
  • Open field test
  • Prenatal cocaine

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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