title: Effects of the histamine H₃ receptor antagonist ABT-239 on cognition and nicotine-induced memory enhancement in mice.
abstract: BACKGROUND
  The strong correlation between central histaminergic and cholinergic pathways on cognitive processes has been reported extensively. However, the role of histamine H(3) receptor mechanisms interacting with nicotinic mechanisms has not previously been extensively investigated.
  
  
  METHODS
  The current study was conducted to determine the interactions of nicotinic and histamine H(3) receptor systems with regard to learning and memory function using a modified elevated plus-maze test in mice. In this test, the latency for mice to move from the open arm to the enclosed arm (i.e., transfer latency) was used as an index of memory. We tested whether ABT-239 (4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl), an H(3) receptor antagonist/inverse agonist, had influence on two different stages of memory, i.e., memory acquisition and consolidation (administered prior to or immediately after the first trial, respectively) and whether ABT-239 influenced nicotine-induced memory enhancement.
  
  
  RESULTS
  Our results revealed that the acute administration of nicotine (0.035 and 0.175 mg/kg), but not of ABT-239 (0.1-3 mg/kg) reduced transfer latency in the acquisition and consolidation phases. In combination studies, concomitant administration of either ABT-239 (1 and 3 mg/kg) and nicotine (0.035 mg/kg), or ABT-239 (0.1 mg/kg) and nicotine (0.0175 mg/kg) further increased nicotine-induced improvement in both memory acquisition and consolidation.
  
  
  CONCLUSIONS
  The present data confirm an important role for H(3) receptors in regulating nicotine-induced mnemonic effects since inhibition of H(3) receptors augmented nicotine-induced memory enhancement in mice.
authors: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4A, PL 20-093 Lublin, Poland.
authors: Marta
authors: M
authors: Kruk
authors: Joanna
authors: J
authors: Miszkiel
authors: Andrew C
authors: AC
authors: McCreary
authors: Edmund
authors: E
authors: Przegaliński
authors: Małgorzata
authors: M
authors: Filip
authors: Grażyna
authors: G
authors: Biała
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D054314:Drug Inverse Agonism; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D001572:Benzofurans; D054828:Histamine H3 Antagonists; D018722:Nicotinic Agonists; D018697:Nootropic Agents; D011759:Pyrrolidines; D018100:Receptors, Histamine H3; D009538:Nicotine; C496397:benzonitrile, 4-(2-(2-((2r)-2-methyl-1-pyrrolidinyl)ethyl)-5-benzofuranyl)-