Nicotine enhances contextual fear conditioning in C57BL/6J mice at 1 and 7 days post-training

Neurobiology of Learning and Memory

Kenney

Gould

2008

Self Cite

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 β2 or α7 nAChR subunit knockout (KO) and corresponding wild-type (WT) mice were withdrawn from 12 days of chronic nicotine treatment (6.3 mg/kg/day), and trained with 2 conditioned stimulus (CS; 85 dB white noise) -unconditioned stimulus (US; 0.57mA 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-beta-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.

Section: Discussionsupporting

confidence: 80%

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

Neurobiology of Learning and Memory

Kenney

Gould

2008

Self Cite

“…In addition, hippocampal lesions disrupt both foreground and background fear conditioning [5,43,51,61]. Finally, studies in our lab have shown that acute nicotine administration enhances contextual fear conditioning regardless of whether the context is a foreground or a background stimulus [14,15,27,25,26,24]. The current study examined if nicotine withdrawal disrupts processes common to both types of contextual conditioning.…”

Section: Introductionmentioning

confidence: 87%

Nicotine withdrawal disrupts both foreground and background contextual fear conditioning but not pre-pulse inhibition of the acoustic startle response in C57BL/6 mice

André

Gulick

Behavioural Brain Research

et al. 2008

Nicotine withdrawal is associated with multiple symptoms such as anxiety, increased appetite, and disrupted cognition in humans. Although animal models have provided insights into the somatic and affective symptoms of nicotine withdrawal, less research has focused on the effects of nicotine withdrawal on cognition. Therefore, in this study, C57BL/6 mice were used to test the effects of withdrawal from chronic nicotine on foreground and background contextual fear conditioning, which present the context as a primary or secondary stimulus, respectively. Mice withdrawn from 12 days of chronic nicotine (6.3 mg/kg/day) or saline were trained and tested in either foreground or background contextual fear conditioning; nicotine withdrawal-associated deficits in contextual fear conditioning were observed in both conditions. Mice were also tested for the effects of withdrawal on pre-pulse inhibition of the acoustic startle reflex (PPI), a measure of sensory gating, and on the acoustic startle reflex. Mice withdrawn from 12 days of chronic nicotine (6.3 or 12.6 mg/kg/day) or saline underwent one 30-minute PPI and startle session; no effect of withdrawal from chronic nicotine on PPI or startle was observed for either dose at 24 hours after nicotine removal. Therefore, mice were tested at different time points following withdrawal from 12.6 mg/kg/day chronic nicotine (8, 24, and 48 hours after nicotine removal). No effect of withdrawal from chronic nicotine was observed at any time point for PPI. Overall, these results demonstrate that nicotine withdrawal disrupts two methods of contextual learning but not sensory gating in C57BL/6 mice.

“…Consistent with these data, research in mice has demonstrated that nicotine alters contextual learning. In mice trained to form an association between an auditory conditioned stimulus (CS) and a footshock unconditioned stimulus (US; cued conditioning), and an association between the training context CS and the US (contextual conditioning), acute nicotine enhances contextual conditioning, but has no effect on cued conditioning [30,32,31,56,55,186]. However, contextual conditioning is not altered by a dose of chronic nicotine that produces the same plasma nicotine levels as the acute dose that produces enhancement, suggesting the development of tolerance [30].…”

Section: Nicotinic Acetylcholine Receptors: Animal Researchmentioning

confidence: 99%

“…Acute nicotine enhances hippocampus-dependent forms of learning, such as trace cued conditioning [56,54] and contextual conditioning [34,57], whereas withdrawal from chronic nicotine produces deficits in contextual conditioning [33,30,132,135]. Research with KO mice has demonstrated that the effects of nicotine on hippocampus-dependent forms of learning require the β2 nAChR subunit.…”

Section: The β2 Nachr Subunitmentioning

confidence: 99%

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

Behavioural Brain Research

Gould

2008

Self Cite

Tobacco smoking is a leading preventable cause of death in the United States and produces a major health and economic burden. Although the majority of smokers want to quit, few are successful. These data highlight the need for additional research into the neurobiology of tobacco dependence. Addiction to nicotine, the main psychoactive component of tobacco, is influenced by multiple factors that include individual differences in genetic makeup. Twin studies have demonstrated that genetic factors can influence vulnerability to nicotine addiction, and subsequent research has identified genes that may alter sensitivity to nicotine. In humans, genome-wide and candidate gene association studies have demonstrated that genes encoding nicotinic acetylcholine receptor (nAChR) proteins are associated with multiple smoking phenotypes. Similarly, research in mice has provided evidence that naturally occurring variability in nAChR genes is associated with changes in nicotine sensitivity. Furthermore, the use of genetic knockout mice has allowed researchers to determine the nAChR genes that mediate the effects of nicotine, whereas research with knockin mice has demonstrated that changes to nAChR genes can dramatically alter nicotine sensitivity. This review will examine the genetic factors that alter susceptibility to nicotine addiction, with an emphasis on the genes that encode nAChR proteins.