, 2003). In addition, ��4?/? mice were insensitive to nicotine-induced seizures and hypolocomotion, had an attenuated nicotine-induced hypothermic response, and did not show somatic selleck screening library signs of nicotine withdrawal (Kedmi, Beaudet, & Orr-Urtreger, 2004; Sack et al., 2005; Salas et al., 2003; Salas, Cook, Bassetto, & De Biasi, 2004a; Salas, Pieri, & De Biasi, 2004b). Furthermore, ��4 null mutation resulted in reduced hyperalgesia during nicotine withdrawal (Salas et al., 2004b), suggesting a role for ��4-containing nAChRs in modulating pain sensitivity. The current study explored the role of ��4-containing nAChRs in regulating learning and memory processes by comparing the performance of ��4+/+ and ��4?/? mice in a variety of cognitive tasks, such as the Barnes circular maze, contextual and cued fear conditioning, and spontaneous alternations in the Y maze.

In addition, we evaluated anxiety-like behavior using the light�Cdark transfer test, compulsive-like behavior using marble burying, and depression-like behavior using the forced swim and tail suspension tests to further characterize the behavioral phenotype of ��4?/? mice. Furthermore, locomotor activity and exploratory behavior were also investigated because many of the cognitive tasks used in this study are based on exploration. Finally, the potential role of ��4-containing nAChRs in mediating nicotine-induced analgesia was investigated by subjecting ��4 knockout mice to two standard assays of noxious heat sensitivity: the tail immersion and hot plate tests. Materials and Methods Animals ��4 nAChR subunit knockout breeder mice were obtained from Drs.

Al Collins and Michael Marks, University of Colorado at Boulder, CO, and these mice were backcrossed to C57BL/6J for at least 10 generations. Male and female WT and knockout littermates used in our study were generated by mating male and female heterozygous parents. Genotypes were determined by polymerase chain reaction. Mice were housed in groups of 2�C4, with food and water available ad libitum except during testing. The animal holding room was maintained on a 12-h light/dark cycle (lights off at 07:00 hr), and behavioral testing occurred during the dark (active) phase.

All experiments Cilengitide were conducted in accordance with the guidelines of the American Association for the Accreditation of Laboratory Animal Care and National Research Council’s Guide for Care and Use of Laboratory Animals and were approved by the University of California San Diego and The Scripps Research Institute Institutional Animal Care and Use Committees. Drugs (?)-Nicotine hydrogen bitartrate salt (Sigma-Aldrich, St. Louis, MO) was dissolved in physiological saline (0.9%; Hospira, Lake Forest, IL) at a concentration of 0.3 mg/ml. The pH was adjusted to 7.2 �� 0.2 using sodium hydroxide, and the solution was sterilized through a 0.