Impact of the metabotropic glutamate receptor7 (mGlu7) allosteric agonist, AMN082, on fear learning and memory and anxiety-like behavior

Jolanta H Kotlinska; Malgorzata Lopatynska-Mazurek; Kinga Gawel; Patrycja Gabka; Malgorzata Jenda-Wojtanowska; Marta Kruk-Slomka; Marta Marszalek-Grabska; Zofia Danilczuk; Ewa Kedzierska; Sylwia Talarek; Joanna Listos; Ewa Gibula-Tarlowska

doi:10.1016/j.ejphar.2019.172512

Impact of the metabotropic glutamate receptor7 (mGlu₇) allosteric agonist, AMN082, on fear learning and memory and anxiety-like behavior

Eur J Pharmacol. 2019 Sep 5:858:172512. doi: 10.1016/j.ejphar.2019.172512. Epub 2019 Jun 28.

Affiliations

¹ Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093, Lublin, Poland. Electronic address: jolanta.kotlinska@umlub.pl.
² Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093, Lublin, Poland.
³ Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland.
⁴ Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093, Lublin, Poland; Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland.

PMID: 31260653
DOI: 10.1016/j.ejphar.2019.172512

Abstract

The present study was conducted to evaluate the influence of AMN082, the metabotropic glutamate receptor subtype 7 (mGlu₇) allosteric agonist on different stages of memory processes connected with fear conditioning in the passive avoidance (PA) learning task in mice and negative emotional state (anxiety-like) induced by ethanol- and morphine-withdrawal in the elevated plus maze (EPM) test in rats. To perform the PA test, AMN082 (1.25, 2.5 and 5 mg/kg, i. p.) was injected to interfere with (or inhibit) acquisition, consolidation, and retrieval processes. The retention latency in each group was recorded using a step-through passive avoidance task 24 h after training. In turn, in ethanol- and morphine-withdrawal rats, the influence of AMN082 on anxiety-like behavior was estimated in the EPM test 24 h- (ethanol) and 72- h (morphine) after the last dose of repeated drug administrations. In all experimental groups, AMN082 at the dose of 5 mg/kg significantly decreased the step-through latency of long-term memory in the PA task. These AMN082 effects were reversed by MMPIP (10 mg/kg), the antagonist of mGlu₇ receptor. AMN082 (2.5 and 5 mg/kg) also decreased ethanol- and morphine withdrawal-induced anxiety-like behavior in the EPM test, and this AMN082 (5 mg/kg) effect was counteracted by MMPIP pretreatment. Taken together, the results show that mGlu₇ is involved in fear learning to the context and anxiety-like state connected with unpleasant experiences after ethanol- and morphine withdrawal in rodents. However, it appears that functional dissociation exists between these two AMN082 effects.

Keywords: AMN082; EPM; Ethanol; Morphine; Passive avoidance; mGlu(7).

MeSH terms

Allosteric Regulation / drug effects
Animals
Anxiety / drug therapy*
Anxiety / physiopathology
Anxiety / psychology
Behavior, Animal / drug effects*
Benzhydryl Compounds / pharmacology*
Benzhydryl Compounds / therapeutic use
Dose-Response Relationship, Drug
Fear / drug effects*
Fear / physiology*
Male
Memory / drug effects*
Memory Consolidation / drug effects
Mice
Rats
Receptors, Metabotropic Glutamate / agonists*
Substance Withdrawal Syndrome / drug therapy

Substances

Benzhydryl Compounds
N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor 7