Biomaterial Database

Impairment of fear memory consolidation and expression by antihistamines. 2013

Ayako Nonaka, and Fumitaka Masuda, and Hiroshi Nomura, and Norio Matsuki

Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008568	Memory	Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D003213	Conditioning, Psychological	Simple form of learning involving the formation, strengthening, or weakening of an association between a stimulus and a response.	Conditioning, Psychology,Psychological Conditioning,Social Learning Theory,Social Learning Theories,Theory, Social Learning
D003990	Dibenzoxepins
D004155	Diphenhydramine	A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects.	Benhydramin,Diphenylhydramin,2-Diphenylmethoxy-N,N-dimethylethylamine,Allerdryl,Benadryl,Benylin,Benzhydramine,Dimedrol,Diphenhydramine Citrate,Diphenhydramine Citrate (1:1),Diphenhydramine Hydrochloride,Diphenylhydramine,Dormin,Citrate, Diphenhydramine,Hydrochloride, Diphenhydramine
D004597	Electroshock	Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states.	Electroconvulsive Shock,Electroconvulsive Shocks,Electroshocks,Shock, Electroconvulsive,Shocks, Electroconvulsive
D005108	Extinction, Psychological	The procedure of presenting the conditioned stimulus without REINFORCEMENT to an organism previously conditioned. It refers also to the diminution of a conditioned response resulting from this procedure.	Psychological Extinction,Extinction (Psychology),Extinctions (Psychology),Extinctions, Psychological,Psychological Extinctions
D005239	Fear	The affective response to an actual current external danger which subsides with the elimination of the threatening condition.	Threat Cues,Threat Sensitivity,Cue, Threat,Fears,Sensitivity, Threat,Threat Cue,Threat Sensitivities
D006633	Histamine Antagonists	Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.	Antihistamine,Antihistamines,Histamine Antagonist,Antagonist, Histamine,Antagonists, Histamine