title: Altered pain sensitivity and morphine-induced anti-nociception in mice lacking CCK2 receptors.
abstract: BACKGROUND
  Cholecystokinin (CCK) interacts with the endopioid system in the regulation of various physiological functions, including the control of pain sensitivity, motor activity and emotional behaviour.
  
  
  OBJECTIVE
  The aim of the present work was to study the pain sensitivity, morphine-induced antinociception and density of opioid receptors in mice lacking CCK(2) receptors.
  
  
  METHODS
  Plantar analgesia and hotplate tests were used to evaluate pain sensitivity and morphine-induced antinociception. The parameters of opioid receptors were analysed by using [(3)H]-diprenorphine binding.
  
  
  RESULTS
  In the plantar analgesia test the latency of hind paw withdrawal was significantly increased in CCK(2) receptor deficient mice compared to wild-type (+/+) littermates. The treatment with saline reversed the reduced pain sensitivity in heterozygous (+/-) and homozygous (-/-) mice. The administration of morphine (1 mg/kg) induced a significantly stronger antinociceptive effect in homozygous (-/-) mice compared with wild-type (+/+) animals. In the hotplate test, only homozygous (-/-) mutant mice displayed the delayed latency of hind paw licking/shaking in comparison with wild-type (+/+) mice. The injection of saline and isolation of mice for 30 min reversed the delayed response in homozygous (-/-) mice. However, in this test, the anti-nociceptive action of morphine (5-10 mg/kg) in mutant mice did not differ from that in wild-type (+/+) littermates. By contrast, the jump latency was decreased in both homozygous (-/-) and heterozygous (+/-) mice in the hotplate test. The increased density of opioid receptors was established in the striatum of homozygous (-/-) mice.
  
  
  CONCLUSIONS
  It is apparent that the targeted mutagenesis of the CCK(2) receptor gene has different effects on the sensitivity of opioid receptors in various brain structures. This is a probable reason for the altered pain sensitivity and morphine-induced antinociception in mutant mice compared to wild-type (+/+) littermates.
authors.affiliation: Department of Physiology, Biomedicum, University of Tartu, 19 Ravila Street, 50411, Tartu, Estonia.
authors.forename: Alar
authors.initials: A
authors.lastname: Veraksits
authors.forename: Kertu
authors.initials: K
authors.lastname: Rünkorg
authors.forename: Kaido
authors.initials: K
authors.lastname: Kurrikoff
authors.forename: Sirli
authors.initials: S
authors.lastname: Raud
authors.forename: Urho
authors.initials: U
authors.lastname: Abramov
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Matsui
authors.forename: Michel
authors.initials: M
authors.lastname: Bourin
authors.forename: Sulev
authors.initials: S
authors.lastname: Kõks
authors.forename: Eero
authors.initials: E
authors.lastname: Vasar
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004174:Diprenorphine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects*; D011869:Radioligand Assay; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D004174:Diprenorphine; D009020:Morphine