title: c-Jun-N-terminal kinase 1 is necessary for nicotine-induced enhancement of contextual fear conditioning.
abstract: Acute nicotine enhances hippocampus-dependent learning. Identifying how acute nicotine improves learning will aid in understanding how nicotine facilitates the development of maladaptive memories that contribute to drug-seeking behaviors, help development of medications to treat disorders associated with cognitive decline, and advance understanding of the neurobiology of learning and memory. The effects of nicotine on learning may involve recruitment of signaling through the c-Jun N-terminal kinase family (JNK 1-3). Learning in the presence of acute nicotine increases the transcription of mitogen-activated protein kinase 8 (MAPK8, also known as JNK1), likely through a CREB-dependent mechanism. The functional significance of JNK1 in the effects of acute nicotine on learning, however, is unknown. The current studies undertook a backward genetic approach to determine the functional contribution JNK1 protein makes to nicotine-enhanced contextual fear conditioning. JNK1 wildtype (WT) and knockout (KO) mice were administered acute nicotine prior to contextual and cued fear conditioning. 24h later, mice were evaluated for hippocampus-dependent (contextual fear conditioning) and hippocampus-independent (cued fear conditioning) memory. Nicotine selectively enhanced contextual conditioning in WT mice, but not in KO mice. Nicotine had no effect on hippocampus-independent learning in either genotype. JNK1 KO and WT mice given saline showed similar levels of learning. These data suggest that JNK1 may be recruited by nicotine and is functionally necessary for the acute effects of nicotine on learning and memory.
authors.affiliation: Temple University Department of Psychology, Neuroscience Program, Temple University, 1701 N. 13th St, Weiss Hall, Philadelphia, PA 19122, USA. Electronic address: prescott.leach@temple.edu.
authors.forename: Prescott T
authors.initials: PT
authors.lastname: Leach
authors.affiliation: Temple University Department of Psychology, Neuroscience Program, Temple University, 1701 N. 13th St, Weiss Hall, Philadelphia, PA 19122, USA. Electronic address: justin.kenney@sickkids.ca.
authors.forename: Justin W
authors.initials: JW
authors.lastname: Kenney
authors.affiliation: Temple University Department of Psychology, Neuroscience Program, Temple University, 1701 N. 13th St, Weiss Hall, Philadelphia, PA 19122, USA. Electronic address: tgould@temple.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Gould
mesh_terms: D000818:Animals; D003214:Conditioning, Classical; D005239:Fear / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000502:physiology*; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine; D048055:Mitogen-Activated Protein Kinase 8
keywords: Acetylcholine; Addiction; Alzheimer’s disease; Cognition; Genetics; Hippocampus; Mitogen-activated protein kinase