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Published on: February 10, 2012
Nicotine preference and affective behavior of Cd81 knockout mice
R Logan Murphy1,2, Laura L Locklear1,3, M Haris Niaz1
1School of Systems Biology, and the Interdisciplinary Program in Neurosciences, George Mason University, Mail Stop 1J1, Institute of Advanced Biomedical Research Building, 10920 George Mason Circle, Manassas, VA, 20110, USA.
Rationale:
Cd81 -/- (knockout) mice have previously been reported to have reduced cocaine preference and increased striatal dopamine content and dopamine turnover, but normal learning and memory in the Morris water maze. The effects of Cd81 on other behaviors and drugs of abuse have not been investigated.
Objectives And Methods:
We measured the effects of Cd81 -/- in a modified two-bottle choice test for nicotine, as well as in somatic signs of nicotine withdrawal, four tests of affective behavior, and tyrosine hydroxylase gene expression assays.
Results:
We found that Cd81 loss-of-function significantly increased voluntary nicotine consumption and somatic signs of nicotine withdrawal. Nicotine consumption of Cd81 -/- female mice increased for 3 weeks and then remained relatively stable for the next 5 weeks, suggesting that their nicotine consumption continued to be limited by aversion to higher nicotine doses. Cd81 -/- also produced a dramatic and significant increase in struggling in the forced swim test and a significant increase in the time spent in the light chamber of the light/dark box. The elevated plus maze and the tail suspension test did not show a main effect of genotype. Therefore, we conclude that Cd81 did not have an overall effect on anxiety- or depression-like behavior. Tyrosine hydroxylase mRNA levels were unchanged.
Conclusions:
Cd81 knockouts have a strongly increased nicotine preference, plus a proactive response to specific stressful situations. Together with reports of increased striatal dopamine content and anecdotal reports of increased aggressiveness, these provide intriguing parallels to some aspects of post-traumatic stress disorder.
Insights
Mice lacking the Cd81 gene show increased nicotine preference and withdrawal symptoms. These findings suggest a potential link between Cd81 and stress-related behaviors, warranting further investigation into its role in addiction and trauma responses.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Genetics
Background:
- Previous research indicated Cd81 knockout mice have altered dopamine levels and cocaine preference.
- The impact of Cd81 on behaviors related to other drugs of abuse remained unexplored.
Purpose of the Study:
- To investigate the effects of Cd81 gene deletion on nicotine consumption and withdrawal.
- To assess the influence of Cd81 on affective behaviors and tyrosine hydroxylase gene expression.
Main Methods:
- Utilized a two-bottle choice test for nicotine preference in Cd81 knockout mice.
- Evaluated somatic signs of nicotine withdrawal and performed four tests for affective behavior.
- Assayed tyrosine hydroxylase gene expression levels.
Main Results:
- Cd81 loss-of-function significantly elevated voluntary nicotine consumption and somatic signs of withdrawal.
- Increased struggling in the forced swim test and light chamber preference in the light/dark box were observed.
- No significant effects on anxiety- or depression-like behaviors were found in the elevated plus maze or tail suspension test. Tyrosine hydroxylase mRNA levels remained unchanged.
Conclusions:
- Cd81 knockout mice exhibit a pronounced increase in nicotine preference and heightened responses to stress.
- These findings, coupled with prior observations of altered dopamine and reports of aggression, suggest parallels with post-traumatic stress disorder.
