Hippocampal nAChRs mediate nicotine withdrawal-related learning deficits

Jennifer A. Davis, Thomas J. Gould

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Nicotine modulation of learning may contribute to its abuse liability. The role of hippocampal nicotinic acetylcholine receptors (nAChRs) in the effects of acute, chronic and withdrawal from chronic nicotine on learning was assessed via intrahippocampal drug infusion in mice. Acute dorsal hippocampal nicotine infusion enhanced contextual fear conditioning. Conversely, chronic intrahippocampal infusion of a matched dose had no effect, and withdrawal from chronic infusion impaired learning. Thus, hippocampal functional adaptation, evidenced by learning deficits during abstinence, occurs with the transition from acute to chronic nicotine exposure. To investigate which hippocampal nAChRs mediate these adaptations, C57BL/6, β2 nAChR subunit knockout (KO), and wildtype (WT) mice treated chronically with systemic nicotine received intrahippocampal dihydro-β-erythroidine (a high affinity nAChR antagonist). Intrahippocampal dihydro-β-erythroidine precipitated learning deficits in all but the KO mice. Therefore, the action of nicotine at hippocampal β2* nAChRs mediates adaptations in hippocampal function that underlie withdrawal deficits in contextual fear conditioning.

Original languageEnglish (US)
Pages (from-to)551-561
Number of pages11
JournalEuropean Neuropsychopharmacology
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2009

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Nicotinic Receptors
Nicotine
Learning
Knockout Mice
Fear
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

Cite this

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Hippocampal nAChRs mediate nicotine withdrawal-related learning deficits. / Davis, Jennifer A.; Gould, Thomas J.

In: European Neuropsychopharmacology, Vol. 19, No. 8, 01.08.2009, p. 551-561.

Research output: Contribution to journalArticle

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