title: Mice lacking the β4 subunit of the nicotinic acetylcholine receptor show memory deficits, altered anxiety- and depression-like behavior, and diminished nicotine-induced analgesia.
abstract: BACKGROUND
  The role of β4-containing nicotinic acetylcholine receptors (nAChRs) in cognition, anxiety, depression, and analgesia in the absence of nicotine is unclear.
  
  
  METHODS
  Wild-type (β4(+/+)) and knockout (β4(-/-)) mice for the nAChR β4 subunit were tested in behavioral tests assessing cognitive function, affective behaviors, and nociception.
  
  
  RESULTS
  There were no learning and memory deficits in β4(-/-) mice compared with β4(+/+) mice during the acquisition of the Barnes maze, contextual fear conditioning, and Y maze tasks. In the Barnes maze memory retention test, male β4(-/-) mice showed reduced use of the spatial search strategy, indicating small spatial memory deficits compared with β4(+/+) mice. In the cue-induced fear conditioning memory retention test, β4(-/-) mice exhibited reduced freezing time compared with β4(+/+) mice. Compared with β4(+/+) mice, β4(-/-) mice exhibited decreased anxiety-like behavior in the light-dark box. Depression-like behavior in β4(-/-) mice was decreased in the tail suspension test and increased in the forced swim test compared with β4(+/+) mice. β4(-/-) mice did not differ from β4(+/+) mice in basal nociception but were less sensitive to the antinociceptive effect of nicotine in 2 tests of acute thermal pain.
  
  
  CONCLUSIONS
  Lack of β4-containing nAChRs resulted in small deficits in hippocampus- and amygdala-dependent memory retention functions. β4-containing nAChRs are involved in anxiety- and depression-like behaviors and contribute to the analgesic effects of nicotine.
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Semenova
authors.forename: Candice
authors.initials: C
authors.lastname: Contet
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Roberts
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
mesh_terms: D000679:Amygdala / Q000502:physiology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal; D003071:Cognition / Q000502:physiology*; D003213:Conditioning, Psychological; D003463:Cues; D003863:Depression / Q000235:genetics*; D005239:Fear; D005260:Female; D007858:Learning / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism
chemical_list: D000700:Analgesics; C486720:Chrnb4 protein, mouse; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D009538:Nicotine