Declaration selleck Axitinib of Interests None declared. Acknowledgments This pilot study emerged from initial discussions between the authors and Dr. Nargis Labib of Cairo University and the late Dr. Mostafa Kamel Mohamed of Ain Shams University. We are grateful for their input to the study design. The Center For Applied Research in Qalyubia governorate, Egypt, recruited the subjects and collected specimens; the authors thank Dr. Fatma Abdel Aziz for directing the field work. Dr. Nabiel N. Mikhail directed the data entry and data management for this study.
Nicotine contained in tobacco is considered to be the main ingredient that leads to addiction in human smokers (Mineur & Picciotto, 2008; Stolerman & Jarvis, 1995). In addition, nicotine induces diverse effects, including improvement of cognitive function (Herman & Sofuoglu, 2010; Levin, 2002; Levin et al.

, 2009; Sarter, Parikh, & Howe, 2009; Sofuoglu, 2010), amelioration of anxiety-like behavior (File, Cheeta, & Kenny, 2000), and analgesia (Marubio et al., 1999). Nicotine binds to nicotinic acetylcholine receptors (nAChRs) throughout the brain. To date, 12 subunits of nAChRs have been identified, nine ��-type (��2�C��10) and three ��-type (��2�C��4) that form structurally and functionally distinct hetero- and homopentametric receptors (Changeux, 2010; Collins, Salminen, Marks, Whiteaker, & Grady, 2009). Genetically modified mice with altered expression of various nAChR subunits have been a useful tool for determining the specific role of nAChR subtypes in neurobehavioral function (Fowler, Arends, & Kenny, 2008; Mineur & Picciotto, 2008).

The focus of the present studies was to evaluate the specific role of ��4-containing nAChRs in cognitive function and nociception using mutant mice null for the ��4 nAChR subunit (��4?/?) and wild-type mice (WT, ��4+/+). ��4-containing nAChRs are widely expressed in the peripheral nervous system (Xu et al., 1999). In the brain, high concentrations of ��4-containing nAChRs are found in the olfactory bulb, medial habenula, pineal gland, interpenduncular nucleus, and inferior colliculus (Gahring, Persiyanov, & Rogers, 2004; Klink, de Kerchove d��Exaerde, Zoli, & Changeux, 2001; Quick, Ceballos, Kasten, McIntosh, & Lester, 1999; Salas, Pieri, Fung, Dani, & De Biasi, 2003).

Considering that the habenulo�Cpeduncular pathway is implicated in cognition (Klemm, 2004; Lecourtier & Kelly, 2007; Lecourtier, Neijt, & Kelly, 2004) and that ��4 nAChRs are also detectable in the hippocampus, amygdala, and cortex (Dineley-Miller & Patrick, 1992; Picciotto, Caldarone, King, & Zachariou, 2000), ��4-containing nAChRs may be involved in cognitive function. However, the specific role Carfilzomib of ��4-containing nAChRs in cognition has not been studied extensively. It has been shown that ��4?/? mice exhibited unaltered contextual learning compared with WT mice (Wehner et al., 2004).