Histaminergic Neurotransmission as a Gateway for the Cognitive Effect of Oleoylethanolamide in Contextual Fear Conditioning.
The integrity of the brain histaminergic system is necessary for the unfolding of homeostatic and cognitive processes through the recruitment of alternative circuits with distinct temporal patterns. We recently demonstrated that the fat-sensing lipid mediator oleoylethanolamide indirectly activates histaminergic neurons to exerts its hypophagic effects. The present experiments investigated whether histaminergic neurotransmission is necessary also for the modulation of emotional memory induced by oleoylethanolamide in a contextual fear conditioning paradigm.



We examined the acute effect of i.p. administration of oleoylethanolamide immediately posttraining in the contextual fear conditioning test. Retention test was performed 72 hours after training. To test the participation of the brain histaminergic system in the cognitive effect of oleoylethanolamide, we depleted rats of brain histamine with an i.c.v. injection of alpha-fluoromethylhistidine (a suicide inhibitor of histidine decarboxylase) or bilateral intra-amygdala infusions of histamine H1 or H2 receptor antagonists. We also examined the effect of oleoylethanolamide on histamine release in the amygdala using in vivo microdialysis.



Posttraining administration of oleoylethanolamide enhanced freezing time at retention. This effect was blocked by both i.c.v. infusions of alpha-fluoromethylhistidine or by intra-amygdala infusions of either pyrilamine or zolantidine (H1 and H2 receptor antagonists, respectively). Microdialysis experiments showed that oleoylethanolamide increased histamine release from the amygdala of freely moving rats.



Our results suggest that activation of the histaminergic system in the amygdala has a "permissive" role on the memory-enhancing effects of oleoylethanolamide. Hence, targeting the H1 and H2 receptors may modify the expression of emotional memory and reduce dysfunctional aversive memories as found in phobias and posttraumatic stress disorder.
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Universitá di Firenze, Firenze, Italy.
Gustavo
G
Provensi
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Universitá di Firenze, Firenze, Italy.
Roberta
R
Fabbri
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Universitá di Firenze, Firenze, Italy.|Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA.
Leonardo
L
Munari
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Universitá di Firenze, Firenze, Italy.
Alessia
A
Costa
Dipartimento di Medicina Sperimentale e Clinica, Universitá di Firenze, Firenze, Italy.
Elisabetta
E
Baldi
Dipartimento di Medicina Sperimentale e Clinica, Universitá di Firenze, Firenze, Italy.
Corrado
C
Bucherelli
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Universitá di Firenze, Firenze, Italy.
Patrizio
P
Blandina
Dipartimento di Scienze della Salute, Universitá di Firenze, Firenze, Italy.
Maria Beatrice
MB
Passani
D000704:Analysis of Variance; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects*; D063388:Endocannabinoids / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000187:drug effects*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D006632:Histamine / Q000378:metabolism*; D018494:Histamine Agents / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology; D017551:Microdialysis; D009829:Oleic Acids / Q000494:pharmacology*; D050198:Phenoxypropanolamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D052160:Benzothiazoles; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D018494:Histamine Agents; D008762:Methylhistidines; D009829:Oleic Acids; D050198:Phenoxypropanolamines; D010880:Piperidines; C488250:oleoylethanolamide; C028309:alpha-fluoromethylhistidine; D006632:Histamine; C055302:zolantidine
alpha-fluoromethylhistidine; emotional memory; in vivo microdialysis; pyrilamine; zolantidine