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

Kotlińska, Jolanta; Łopatyńska-Mazurek, Małgorzata; Gaweł, Kinga; Gabka, Patrycja; Jenda-Wojtanowska, Malgorzata; Kruk-Słomka, Marta; Marszałek‐Grabska, Marta; Danilczuk, Zofia; Kędzierska, Ewa; Talarek, Sylwia; Listos, Joanna; Gibuła‐Tarłowska, Ewa

doi:10.1016/j.ejphar.2019.172512

Cited by 13 publications

(13 citation statements)

References 65 publications

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“…Thus, activation or inhibition of mGlu7 can change the balance of excitatory and inhibitory neurotransmitter release in the same way or differently, leading to similar or different social behavioral traits, respectively. However, the observed effects are not mediated via alterations in general activity of the females, because neither AMN082 nor XAP044 affects locomotor activity 36,52…”

Section: Discussionmentioning

confidence: 96%

“…However, the observed effects are not mediated via alterations in general activity of the females, because neither AMN082 nor XAP044 affects locomotor activity. 36,52 With respect to maternal aggression, genetic mGlu7 ablation caused decreased spontaneous maternal aggression, whereas blocking mGlu7 in lactating CD1 mice increased this behavior. 55 Moreover, male mice lacking mGlu7 display a strong reduction in intermale aggression toward an intruder, probably caused by olfactory deficits.…”

Section: Discussionmentioning

confidence: 99%

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Metabotropic glutamate receptor subtype 7 controls maternal care, maternal motivation and maternal aggression in mice

Gryksa

Mittmann

Bauer

et al. 2019

Genes Brain and Behavior

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The group III metabotropic glutamate receptor subtype 7 (mGlu7) is an important regulator of glutamatergic and GABAergic neurotransmission and known to mediate emotionality and male social behavior. However, a possible regulatory role in maternal behavior remains unknown to date. Adequate expression of maternal behavior is essential for successful rearing and healthy development of the young. By understanding genetic and neural mechanisms underlying this important prosocial behavior, we gain valuable insights into possible dysregulations. Using genetic ablation as well as pharmacological modulation, we studied various parameters of maternal behavior in two different mouse strains under the influence of mGlu7. We can clearly show a regulatory role of mGlu7 in maternal behavior. Naïve virgin female C57BL/6 mGlu7 knockout mice showed more often nursing postures and less spontaneous maternal aggression compared to their heterozygous and wildtype littermates. In lactating C57BL/6 wildtype mice, acute central activation of mGlu7 by the selective agonist AMN082 reduced arched back nursing and accelerated pup retrieval without affecting maternal aggression. In addition, in lactating CD1 wildtype mice the selective mGlu7 antagonist XAP044 increased both pup retrieval and maternal aggression. With respect to receptor expression levels, mGlu7 mRNA expression was higher in lactating vs virgin C57BL/6 mice in the prefrontal cortex, but not hypothalamus or hippocampus. In conclusion, these findings highlight a significant role of the mGlu7 receptor subtype in mediating maternal behavior in mice. Region-dependent studies are warranted to further extend our knowledge on the specific function of the brain glutamate system in maternal behavior.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Metabotropic glutamate receptor subtype 7 controls maternal care, maternal motivation and maternal aggression in mice

Gryksa

Mittmann

Bauer

et al. 2019

Genes Brain and Behavior

View full text Add to dashboard Cite

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“…also decreased ethanol-and morphine withdrawal-induced anxiety-like behavior in the elevated plus maze test. 10 AMN082 at a dose of 10 mg/kg I.P. suppressed the locomotor effect of both cocaine-or morphine-induced hyperactivity.…”

Section: Dosage and Time Course Of Amn082 Treatmentmentioning

confidence: 91%

“…6 Its metabolite Met-1 has approximately 100-fold greater a nity than AMN082 for binding to the mGlu7 receptor. 7 Its action on the CNS has demonstrated anti-anxiety and antidepressive effects [8][9][10] and antiparkinsonianlike effects, 11 and it is used in the treatment of cocaine or opioid addiction. 12 These mechanisms include regulating glutamate release at the synapse, 13 binding to the serotonin transporter, 6 activation of prosurvival MAPK/ERK 1/2 and PI3-K/Akt pathways, 14 and stimulated mammalian target of rapamycin (mTOR) activation.…”

Section: Introductionmentioning

confidence: 99%

The neuroprotective effects of AMN082 on neuronal apoptosis in rat after traumatic brain injury

Wang

Lee

et al. 2020

Preprint

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The aim of this study is to investigate whether the neuroprotective effect of AMN082 is via attenuating glutamic receptor associated neuronal apoptosis and improves functional outcomes after traumatic brain injury (TBI). Anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 was intraperitoneally injected (10 mg/kg) at 0, 24, and 48 hr after TBI. During the 120 minutes after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. The motor function, infarction volume, and neuronal nitrosative stress-associated apoptosis, N-Methyl-D-aspartate receptor 2A (NR2A) and NR2B expression were measured on the 3rd day after TBI. The results showed AMN082-treated group had the lower ICP and higher CPP after TBI. The TBI-induced motor deficits, increased infarction volume, neuronal apoptosis, 3-nitrotyrosine and inducible nitric oxide synthase expression in the peri-contusion cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased the NR2A and NR2B expression in neuronal cells. We concluded intraperitoneal injection of AMN082 for 3 days may ameliorate TBI insults by attenuating glutamic receptor associated nitrosative stress and neuronal apoptosis in the peri-contusion cortex. We suggest AMN082 administration in acute stage may be a promising strategy for TBI.

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“…Furthermore, AMN082 has been shown to affect the CNS to exert anti-anxiety, antidepressive effects [ 17 – 19 ] and antiparkinsonian-like effects [ 20 ], and it is used in the treatment of cocaine or opioid addiction [ 21 ]. Its mechanisms include regulating glutamate release at the synapse [ 22 ], binding to the serotonin transporter [ 10 ], activating prosurvival MAPK/ERK 1/2 and PI3-K/Akt pathways [ 15 ], and stimulating mammalian target of rapamycin (mTOR) activation [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury

Nyam

Kuo

et al. 2021

BMC Neurosci

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Background The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). Methods Anesthetized male Sprague–Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-d-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI. Results The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells. Conclusions We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.

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

Cited by 13 publications

References 65 publications

Metabotropic glutamate receptor subtype 7 controls maternal care, maternal motivation and maternal aggression in mice

Metabotropic glutamate receptor subtype 7 controls maternal care, maternal motivation and maternal aggression in mice

The neuroprotective effects of AMN082 on neuronal apoptosis in rat after traumatic brain injury

The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury

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