Thyroid Receptor β is Critically Involved in the Effects of Nicotine on Hippocampus-Dependent Memory

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 414-436-HPT Axis Biology & Action
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-424
Prescott Tarn Leach*1, Justin W. Kenney2, David Connor1 and Thomas J. Gould1
1Temple University, Philadelphia, PA, 2University of Southampton, Southampton, United Kingdom
Cigarette smoking is common despite its adverse effects on health (1, 2). Nicotine’s effects on cognition may contribute to the development of addiction to tobacco products by enhancing maladaptive drug-context associations (3, 4). Examination with Protein/DNA arrays (Panomics) identified hippocampal thyroid receptor (TR) activation during nicotine enhancement of hippocampus-dependent learning. The present work evaluates the functional contribution of TRs (β and α1) in the effect of nicotine on hippocampus-dependent memory using a contextual fear conditioning paradigm. It was hypothesized that TRs would be critical for the acute effects of nicotine on contextual fear conditioning. To determine the role of TRβ and TRα1 in the effects of nicotine on memory, mice lacking the TRβ and TRα1 gene (KOs) and wildtype littermates (WTs) were administered nicotine prior to contextual fear conditioning. Twenty-four hours later, mice were returned to the training context and evaluated for context-evoked freezing for 5 minutes. For TRβ mutants, WTs receiving nicotine froze more than WTs receiving vehicle alone, while KOs receiving nicotine did not differ from vehicle treated mice. This demonstrates a critical role for TRβ in the effect of nicotine on hippocampus-dependent memory. For TRα1 mutants, WTs and KOs receiving nicotine froze significantly more than those receiving vehicle, indicating this receptor is not important for the pro-cognitive effects of nicotine. Analysis of serum thyroid hormone levels after acute nicotine administration and after cessation from chronic nicotine treatment revealed that nicotine withdrawal significantly reduces thyroid hormone levels.  Disrupted thyroid hormone signaling may lead to a subclinical hypothyroid condition that could contribute to nicotine withdrawal-related symptoms.

1. Swan, G.E. and C.N. Lessov-Schlaggar, The effects of tobacco smoke and nicotine on cognition and the brain. Neuropsychol Rev, 2007. 17(3): p. 259-73. 2. Ockene, I.S. and N.H. Miller, Cigarette smoking, cardiovascular disease, and stroke: a statement for healthcare professionals from the American Heart Association. American Heart Association Task Force on Risk Reduction. Circulation, 1997. 96(9): p. 3243-7. 3. Gould, T.J., Nicotine and hippocampus-dependent learning: implications for addiction. Mol Neurobiol, 2006. 34(2): p. 93-107. 4. Kenney, J.W. and T.J. Gould, Modulation of hippocampus-dependent learning and synaptic plasticity by nicotine. Mol Neurobiol, 2008. 38(1): p. 101-21.

Nothing to Disclose: PTL, JWK, DC, TJG

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Sources of Research Support: National Institute on Drug Abuse (TJG, DA017949) and National Institute on Drug Abuse training grant (JWK and PTL, DA07237)