Levin ED, Petro A, Rezvani AH, Pollard N, Christopher NC, Strauss M et al.. Nicotinic alpha7- or beta2-containing receptor knockout: effects on radial-arm maze learning and long-term nicotine consumption in mice. Behav Brain Res 196: 207-213

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
Behavioural brain research (Impact Factor: 3.03). 10/2008; 196(2):207-13. DOI: 10.1016/j.bbr.2008.08.048
Source: PubMed


Classically, it has been thought that high-affinity nicotinic receptors-containing beta2 subunits are the most important receptor subtypes for nicotinic involvement in cognitive function and nicotine self-administration, while low affinity alpha7-containing nicotinic receptors have not been thought to be important. In the current study, we found that knockout of either beta2 or alpha7 subunits caused significant deficits in spatial discrimination in mice. The character of the impairment in the two knockouts was different. The beta2 knockout preferentially impaired cognition in males while the alpha7 caused impairment regardless of sex. Both beta2- and alpha7-containing nicotinic receptors also are important for nicotine self-administration, also in different ways. Most animal model studies of nicotine self-administration are relatively short-term whereas the problem of tobacco addiction is considerably longer-term. To better model the impact of nicotinic receptor subtypes on nicotine self-administration over the long-term, we studied the impact of genetic knockout of low affinity alpha7 receptors vs. high-affinity beta2-containing nicotinic receptors. Mice with knockouts of either of these receptors and their wildtype counter parts were given free access to a choice of nicotine-containing and nicotine-free solution in their home cages on a continuous basis over a period of 5 months. During the first few weeks, the beta2-containing nicotinic receptor knockout mice showed a significant decrease in nicotine consumption relative to wildtype mice, whereas the alpha7 knockout mice did not significantly differ from wildtype controls at the beginning of their access to nicotine. Interestingly, in the longer-term after the first few weeks of nicotine access, the beta2 knockout mice returned to wildtype mouse levels of nicotine consumption, whereas the alpha7 knockout mice developed an emergent decrease in nicotine consumption. The alpha7 receptor knockout-induced decrease in nicotine consumption persisted for the 5-month period of the study. Both alpha7- and beta2-containing nicotinic receptors play critical roles in cognitive function and nicotine self-administration. Regarding cognitive function, beta2-containing receptors are important for maintaining normal sex differences in spatial learning and memory, whereas alpha7 receptors are important for cognitive function regardless of sex. Regarding nicotine self-administration high-affinity beta2-containing nicotinic receptors are important for consumption during the initial phase of nicotine access, but it is the alpha7 nicotinic receptors that are important for the longer-term regulation of nicotine consumption.

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Available from: Amir H Rezvani, Oct 13, 2014
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    • "The formation of new memories in the hippocampus is influenced by nicotinic receptor function. This is exemplified by observations that the encoding of memories can be enhanced by the exogenous activation of nicotinic receptors (Davis and Gould, 2006; Levin et al., 2009) Frontiers in Cellular Neuroscience | 1 April 2015 | and memory performance can be impaired by the injection of α4β2 * ( nicotinic receptors that contain α4 and β2 subunits but may include other types of subunits ) or α7 nicotinic receptor antagonists directly into the hippocampus ( Levin , 2002 ) . Furthermore , dysfunction of both α4 and β2 nicotinic subunits in the hippocampus have been correlated with memory impairment associated with addiction , neurodegenerative disease and aging . "
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    • "Activation of nicotinic receptors in the hippocampus has a significant impact on physiological and pathophysiological memory formation (Levin, 2002; Levin et al., 2002, 2009; Buccafusco et al., 2005; Davis and Gould, 2006, 2009; Nott and Levin, 2006; Davis et al., 2007). Of the 11 different nicotinic receptor subunits found in the mammalian CNS, 9 have been reported to be expressed in hippocampal CA1 neurons (Sudweeks and Yakel, 2000). "
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    • "e l s e v i e r . c o m / l o c a t e / y m c n e et al., 2006; Hellier et al., 2012; Levin et al., 2009; Young et al., 2007, 2011). These findings suggest crucial roles of α7 nAChR in cortical circuit function and dysfunction. "
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