title: Impairment of fear memory consolidation and expression by antihistamines.
abstract: Antihistamines are widely used to treat allergy symptoms. First-generation antihistamines have adverse effects on the central nervous system (CNS), such as hypnotic and amnesic effects, whereas second-generation antihistamines have poor brain penetration, and therefore, have fewer CNS-related adverse effects. Memory consists of several phases, including acquisition, consolidation, expression, and extinction. It remains unclear whether these phases are affected by antihistamines. We investigated the effects of diphenhydramine, a first-generation antihistamine, and levocetirizine and olopatadine, second-generation antihistamines, on memory phases. Mice were subjected to fear conditioning on day 1 and tested on day 2. Antihistamines were administered before conditioning, immediately after conditioning, or before the test session. Diphenhydramine (30mg/kg) decreased freezing time when administered immediately after conditioning or before the test session. These effects were not attributable to a change in locomotor activity. Levocetirizine (0.1, 1, 10mg/kg) and olopatadine (1, 10, 20mg/kg) had no effects on conditioned fear. We also examined the effect of diphenhydramine and levocetirizine on the expression of an activity-dependent gene associated with the test session. Diphenhydramine, but not levocetirizine, increased Arc transcription in the central nucleus of the amygdala. These data indicate that diphenhydramine, but not levocetirizine or olopatadine, impairs the consolidation and expression of conditioned fear.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nonaka
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Masuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nomura
authors.forename: Norio
authors.initials: N
authors.lastname: Matsuki
mesh_terms: D000679:Amygdala / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D017332:Cetirizine / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D003990:Dibenzoxepins / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004597:Electroshock; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D006633:Histamine Antagonists / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D000069605:Olopatadine Hydrochloride
chemical_list: D003990:Dibenzoxepins; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D039563:Histamine H1 Antagonists, Non-Sedating; D000069605:Olopatadine Hydrochloride; C472067:levocetirizine; D004155:Diphenhydramine; D017332:Cetirizine