Acetaldehyde, a major constituent of tobacco smoke, enhances behavioral, endocrine, and neuronal responses to nicotine in adolescent and adult rats

Junran Cao, James D. Belluzzi, Sandra E. Loughlin, Daniel E. Keyler, Paul R. Pentel, Frances M. Leslie

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


We have previously shown that acetaldehyde, a constituent of tobacco smoke, increases nicotine self-administration in adolescent, but not adult, rats. The aim of this study was to determine whether acetaldehyde influences other behavioral, endocrine, or neuronal responses to nicotine at either age. Juvenile (postnatal day (P) 27) and adult (P90) male Sprague-Dawley rats were treated with saline, acetaldehyde (16 μg/kg/injection × 2, i.v.), nicotine (30 μg/kg/injection × 2, i.v.) or a combination of acetaldehyde and nicotine. Locomotion and center time were evaluated for 30 min in a novel open field, before measurement of plasma corticosterone levels and brain c-fos mRNA. Nicotine increased locomotor activity in juveniles but decreased it in adults; in contrast, center time was increased at both ages. Acetaldehyde potentiated nicotine's locomotor effects, but not center time. Nicotine induced c-fos expression in the bed nucleus of the stria terminalis, the central nucleus of the amygdala (CeA), nucleus accumbens, and the superior colliculus (SC) at both ages, whereas it activated the hypothalamic paraventricular nucleus (PVN) and consequent corticosterone secretion only in adults. Acetaldehyde potentiated nicotine-induced c-fos in CeA and SC, and activation of PVN c-fos expression/plasma corticosterone release; however, this drug interaction was only observed in behaviorally tested animals, not those that were minimally stressed. Thus, acetaldehyde may modulate the interaction of nicotine and stress. Although pharmacokinetic studies showed that acetaldehyde did not change nicotine levels in either brain or serum, nicotine penetration into the brain was slower in juveniles as compared to adults.

Original languageEnglish (US)
Pages (from-to)2025-2035
Number of pages11
Issue number9
StatePublished - Sep 2007

Bibliographical note

Funding Information:
We thank Yiling Chen, MD, and Ruihua Wang, MD for their assistance. This study is supported by DA 19138 and DA 21267.


  • Age
  • Anxiety
  • C-fos
  • Locomotion
  • Paraventricular nucleus
  • Stress


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