Provided herein are transgenic non-human animals having a transgene encoding a variant nicotinic acetylcholine receptor (nAChR) subunit, wherein the variant nAChR subunit is selected from the group consisting of α6, α5, and β2. The transgenic animals display a modified phenotype that includes nicotinic hypersensitivity. Also provided are methods of generating the invention transgenic animals. Further provided are methods for screening a candidate agent for the ability to modulate nicotine-mediated behavior in the invention transgenic animals.
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