Effects of continuous oral nicotine administration on brain nicotinic receptors and responsiveness to nicotine in C57B1/6 mice

J. A. Sparks, J. R. Pauly

Research output: Contribution to journalArticlepeer-review

168 Scopus citations

Abstract

The route of drug delivery is an important consideration in studies that evaluate the long-term biobehavioral adaptations that occur in response to chronic drug administration. Continuous infusions (intravenous or subcutaneous) or intermittent intraperitoneal (or subcutaneous) injections are the most commonly utilized routes of chronic drug delivery in these studies. The purpose of the present study was to determine the effects of chronic oral nicotine exposure on sensitivity to nicotine and brain nicotinic cholinergic receptors in female C57B1/6 mice. Mice were randomized to different treatment groups that received 2% saccharin, containing 0-200 μg/ml nicotine (free base). In preliminary experiments, radiotelemetry devices were implanted in the mice; consumption of the nicotine-containing drinking solution caused a significant increase in home-cage nocturnal (but not diurnal) activity and also altered circadian alterations in body temperature. Oral nicotine exposure resulted in dose-related elevations in plasma levels of cotinine, a primary nicotine metabolite. Continuous exposure (30 days) to oral nicotine (200 μg/ml) resulted in the expression of significant tolerance to the locomotor depressant and hypothermic actions of acute nicotine challenge. This tolerance was accompanied by a significant increase in brain nicotinic receptor number assessed by quantitative autoradiography using [3H]-cytisine (α4 nAChr) and [125I]-α- bungarotoxin (α7 nAChr) as radioligands. These results suggest that chronic oral nicotine delivery to female C57B1/6 mice results in behavioral and biochemical changes that resemble changes that occur following other routes of chronic nicotine delivery.

Original languageEnglish
Pages (from-to)145-153
Number of pages9
JournalPsychopharmacology
Volume141
Issue number2
DOIs
StatePublished - 1999

Keywords

  • Autoradiography
  • Circadian rhythm
  • Cytisine
  • Nicotine
  • Oral
  • Tolerance
  • α-Bungarotoxin

ASJC Scopus subject areas

  • Pharmacology

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