β2 subunit containing acetylcholine receptors mediate nicotine withdrawal deficits in the acquisition of contextual fear conditioning

George S. Portugal, Justin W. Kenney, Thomas J. Gould

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Acute nicotine enhances contextual fear conditioning, whereas withdrawal from chronic nicotine produces impairments. However, the nicotinic acetylcholine receptors (nAChR) that are involved in nicotine withdrawal deficits in contextual fear conditioning are unknown. The present study used genetic and pharmacological techniques to investigate the nAChR subtype(s) involved in the effects of nicotine withdrawal on contextual fear conditioning. β2 or α7 nAChR subunit knockout (KO) and corresponding wild-type (WT) mice were withdrawn from 12 days of chronic nicotine treatment (6.3 mg/kg/day), and trained with 2 conditioned stimulus (CS; 85 dB white noise)-unconditioned stimulus (US; 0.57 mA footshock) pairings on day 13. On day 14, mice were tested for contextual and cued freezing. β2 KO mice did not show nicotine withdrawal-related deficits in contextual fear conditioning, in contrast to WT mice and α7 KO mice. A follow-up study investigated if nicotine withdrawal disrupts acquisition or recall of contextual fear conditioning. The high affinity nAChR antagonist dihydro-β-erythroidine (DHβE; 3 mg/kg) was administered prior to training or testing to precipitate withdrawal in chronic nicotine-treated C57BL/6 mice. Deficits in contextual fear conditioning were observed in chronic nicotine-treated mice when DHβE was administered prior to training, but not when administered at testing. These results indicate that β2-containing nAChRs, such as the α4β2 receptor, mediate nicotine withdrawal deficits in contextual fear conditioning. In addition, nicotine withdrawal selectively affects acquisition but not recall or expression of the learned response.

Original languageEnglish (US)
Pages (from-to)106-113
Number of pages8
JournalNeurobiology of Learning and Memory
Volume89
Issue number2
DOIs
StatePublished - Feb 1 2008

Fingerprint

Cholinergic Receptors
Nicotine
Fear
Nicotinic Receptors
Knockout Mice
Conditioning (Psychology)
Genetic Techniques
Cholinergic Antagonists
Inbred C57BL Mouse
Freezing
Pharmacology

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Experimental and Cognitive Psychology

Cite this

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title = "β2 subunit containing acetylcholine receptors mediate nicotine withdrawal deficits in the acquisition of contextual fear conditioning",
abstract = "Acute nicotine enhances contextual fear conditioning, whereas withdrawal from chronic nicotine produces impairments. However, the nicotinic acetylcholine receptors (nAChR) that are involved in nicotine withdrawal deficits in contextual fear conditioning are unknown. The present study used genetic and pharmacological techniques to investigate the nAChR subtype(s) involved in the effects of nicotine withdrawal on contextual fear conditioning. β2 or α7 nAChR subunit knockout (KO) and corresponding wild-type (WT) mice were withdrawn from 12 days of chronic nicotine treatment (6.3 mg/kg/day), and trained with 2 conditioned stimulus (CS; 85 dB white noise)-unconditioned stimulus (US; 0.57 mA footshock) pairings on day 13. On day 14, mice were tested for contextual and cued freezing. β2 KO mice did not show nicotine withdrawal-related deficits in contextual fear conditioning, in contrast to WT mice and α7 KO mice. A follow-up study investigated if nicotine withdrawal disrupts acquisition or recall of contextual fear conditioning. The high affinity nAChR antagonist dihydro-β-erythroidine (DHβE; 3 mg/kg) was administered prior to training or testing to precipitate withdrawal in chronic nicotine-treated C57BL/6 mice. Deficits in contextual fear conditioning were observed in chronic nicotine-treated mice when DHβE was administered prior to training, but not when administered at testing. These results indicate that β2-containing nAChRs, such as the α4β2 receptor, mediate nicotine withdrawal deficits in contextual fear conditioning. In addition, nicotine withdrawal selectively affects acquisition but not recall or expression of the learned response.",
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β2 subunit containing acetylcholine receptors mediate nicotine withdrawal deficits in the acquisition of contextual fear conditioning. / Portugal, George S.; Kenney, Justin W.; Gould, Thomas J.

In: Neurobiology of Learning and Memory, Vol. 89, No. 2, 01.02.2008, p. 106-113.

Research output: Contribution to journalArticle

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AB - Acute nicotine enhances contextual fear conditioning, whereas withdrawal from chronic nicotine produces impairments. However, the nicotinic acetylcholine receptors (nAChR) that are involved in nicotine withdrawal deficits in contextual fear conditioning are unknown. The present study used genetic and pharmacological techniques to investigate the nAChR subtype(s) involved in the effects of nicotine withdrawal on contextual fear conditioning. β2 or α7 nAChR subunit knockout (KO) and corresponding wild-type (WT) mice were withdrawn from 12 days of chronic nicotine treatment (6.3 mg/kg/day), and trained with 2 conditioned stimulus (CS; 85 dB white noise)-unconditioned stimulus (US; 0.57 mA footshock) pairings on day 13. On day 14, mice were tested for contextual and cued freezing. β2 KO mice did not show nicotine withdrawal-related deficits in contextual fear conditioning, in contrast to WT mice and α7 KO mice. A follow-up study investigated if nicotine withdrawal disrupts acquisition or recall of contextual fear conditioning. The high affinity nAChR antagonist dihydro-β-erythroidine (DHβE; 3 mg/kg) was administered prior to training or testing to precipitate withdrawal in chronic nicotine-treated C57BL/6 mice. Deficits in contextual fear conditioning were observed in chronic nicotine-treated mice when DHβE was administered prior to training, but not when administered at testing. These results indicate that β2-containing nAChRs, such as the α4β2 receptor, mediate nicotine withdrawal deficits in contextual fear conditioning. In addition, nicotine withdrawal selectively affects acquisition but not recall or expression of the learned response.

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