Negative allosteric modulation of mGlu7 disrupts fear memory reconsolidation and glutamatergic signaling in rat and human brain tissue
Alexandru Cristian Ciobanu, David Mota Caseiro, Ruifang Niu, Rodrigo Triana del Rio, Cédric Leroux, Alessio Stefanelli, Carmen Flores Nakandakare, Etienne Pralong, Roy T. Daniel, Robert Lütjens, Erwin H. van den Burg, Ron Stoop
TL;DR
A drug that blocks mGlu7 receptors disrupts fear memory in rats and affects glutamate signaling, suggesting a new treatment for anxiety disorders.
Contribution
ADX71743, a specific mGlu7 modulator, disrupts fear memory reconsolidation and alters glutamatergic signaling in rat and human brain tissue.
Findings
ADX71743 disrupts fear memory reconsolidation in rats when administered in the lateral amygdala or subcutaneously.
ADX71743 increases spontaneous excitatory postsynaptic currents and alters glutamate release in rat and human brain tissue.
ADX71743 prevents long-term potentiation at thalamus-to-amygdala synapses under high stimulation conditions.
Abstract
Anxiety- and stress-related disorders are amongst the most frequent neurological disorders, and efficient treatment is lacking. Metabotropic glutamate receptors (mGlu) have emerged as promising targets for intervention. Of particular interest is mGlu7, because of its expression in the lateral amygdala (LA), a region critical for fear learning. In the present study we examined the effects of the highly specific negative allosteric modulator of mGlu7 (ADX71743) on fear memory reconsolidation. Our investigation unveils that infusion in rats of ADX71743 in the LA or subcutaneously disrupts the reconsolidation of fear memories. This effect on reconsolidation was specific to the conditioned stimulus (CS), required fear memory recall, occurred in a defined time window after recall, and significantly decreased reinstatement of fear. Moreover, in ex vivo experiments, ADX71743 disinhibited…
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Taxonomy
TopicsNeuroscience and Neuropharmacology Research · Memory and Neural Mechanisms · GABA and Rice Research