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. 2022 Sep 28;23(19):11423. doi: 10.3390/ijms231911423

Table 3.

Summary of studies on the expression of postsynaptic Glu receptors (NMDAR, AMPAR and GluR5) in rat models of depression and/or after antidepressants treatment.

Postsynaptic Proteins Species/Strain Model/Treatment/Groups Brain Region Methods Findings Authors’ Names
NMDA receptor complex
GluN2A-B Sprague Dawley male and female rats
  • Learned helpless (LH)

  • non-learned helpless (NLH)

  • wild type (WT)

Hippocampus Western blot
Post-embedding Immunogold
↓GluN2A/GluN2B protein in LH compared to NLH
↑GluN2B protein in LH compared to WT
↔GluN2B protein in NLH compared to WT
Bieler et al. [143]
NMDAR
(no information on subunits)
Sprague Dawley male rats
  • Chronic unpredictable mild stress—3 weeks (CUMS)

  • Paroxetine 1.8 mg/kg/d p.o. (PAR) every day from the 4th week

  • Zn 2.3 mg/kg/d p.o. (Zn) every day from the 4th week

  • Folic acid 21 μg/kg/d p.o. (FA) every day from the 4th week

Frontal cortex qPCR ↓NMDAR mRNA after CUMS
↑NMDAR mRNA n after CUMS+ PAR, CUMS+ Zn+ FA, CUMS+ Zn+ FA+ PAR
Dou et al. [144]
GluN1
GluN2A
pT1325-GluN2A
GluN2B
pS1303-GluN2B
Sprague Dawley male rats
  • Chronic unpredictable stress—28 days (CUS)

  • CUS + Ifenprodil (IFE) 3.0 mg/kg i,p.

  • CUS + TC-DAPK 6 (an inhibitor of DAPK1) 290 nM; 0.5 μL/side, microinjected in the mPFC

  • DAPK1 knockdown by adeno-associated virus mediated short hairpin RNA (AAV-shDAPK1), intra-PFC infusion

Medial prefrontal cortex (mPFC) Western blot ↑GluN1, GluN2B, p-GluN2B and ↔ GluN2A,
p-GluN2A protein after CUS
↔GluN2A, p-GluN2A, GluN2B and ↓p-GluN2B protein after CUS+ IFE
↑GluN1 protein after CUS+ IFE
↔GluN1 protein level after CUS+TC-DAPK 6
↔GluN2B and ↓p-GluN2B protein level after CUS+TC-DAPK 6
↔GluN1 protein level after CUS+ AAV-shDAPK1
↔GluN2B protein after CUS+ AAV-shDAPK1
↓p-GluN2B protein after CUS+ AAV-shDAPK1
Li et al. [145]
GluN2A-B Flinders Sensitive Line (FSL) male rats
Flinders Resistant Line (FRL) male rats
  • FSL

  • FRL

Hippocampus (HP)
Prefrontal cortex (PFC)
Western blot ↓GluN2A and ↑GluN2B protein in FSL—HP
↔GluN2A and GluN2B protein in FSL—PFC
Treccani et al. [146]
GluN2A-B Sprague Dawley male rats
  • Olfactory bulbectomy (OB)

  • Sham-operated rats (Sham)

  • Magnesium hydroaspartate 15 mg/kg i.p. (calculated as magnesium ions; Mg15) once daily for 14 days

Prefrontal cortex (PFC)
Hippocampus (HP)
Amygdala (AMY)
Western blot
qPCR
↔GluN2A protein after OB in PFC vs. Sham
↔GluN2A protein after OB+ Mg15 in PFC vs. OB
↔GluN2B protein after OB in PFC vs. Sham
↔GluN2B protein after OB+ Mg15 in PFC vs. OB
↔GluN2A protein after OB in HP vs. Sham
↔GluN2A protein after OB+ Mg15 in HP vs. OB
↔GluN2B protein after OB in HP vs. Sham
↔GluN2B protein after OB+ Mg15 in HP vs. OB
↔GluN2A protein after OB in AMY vs. Sham ↔GluN2A protein after OB+ Mg15 in AMY vs. OB
↔GluN2B protein after OB in AMY vs. Sham
↑GluN2B protein after OB+ Mg15 in AMY vs. OB
Grin2A mRNA after OB in PFC vs. Sham
Grin2A mRNA after OB+ Mg15 in PFC vs. OB
Grin2B mRNA after OB in PFC vs. Sham
Grin2B mRNA after OB+ 15 Mg15 in PFC vs. OB
Grin2A mRNA after OB in HP vs. Sham
Grin2A mRNA after OB+ Mg15 in HP vs. OB
Grin2B mRNA after OB in HP vs. Sham
Grin2B mRNA after OB+ Mg15 in HP vs. OB
Pochwat et al. [147]
GluN1
GluN2A-B
Sprague Dawley male rats
  • Zinc deficiency (ZnD; 3 mg Zn/kg) for 6 weeks

  • Zinc adequate (ZnA; 50 mg Zn/kg)

  • Fluoxetine

10 mg/kg i,p. (FLU) after 4 weeks ZnD for subsequent 2 weeks
Hippocampus Western blot ↑GluN1, GluN2A and GluN2B proteins after ZnD vs. ZnA
↓GluN1, GluN2A and GluN2B proteins after ZnD+ FLU vs. ZnD
Doboszewska et al. [73]
GluN2A-B Sprague Dawley male rats
  • Chronic restraint stress—14 days (CRS)Fasudil 10 mg/kg i.p. (FAS) for 18 days from the 5th day of CRS

Hippocampus
(whole tissue lysate)
Hippocampus
(synaptoneurosomes)
Western blot ↓GluN2A and ↔GluN2B
protein after CRS
↔ GluN2A, ↔GluN2B protein after CRS+ FAS
↔GluN2A, GluN2B protein after CRS
↔GluN2A, GluN2B protein after CRS+ FAS
Román-Albasini et al. [148]
GluN2B Sprague Dawley male rats
  • CUMS—3 weeks

  • inta-CA1 microinjections of BDNF (0.25 μg/μL) for CUMS

  • inta-CA1 microinjections of proBDNF (0.5 μg/μL) for naïve control

Hippocampus Western blot ↔ GluN2B protein after CUMS
↑GluN2B protein after CUMS+BDNF
↓GluN2B protein after proBDNF
Qiao et al. [149]
GluN2B Sprague Dawley male rats
  • CUMS—4 weeks

  • YY-21 10 mg/kg i.g. once a day for 3 weeks after CUMS

  • Fluoxetine 10 mg/kg i.p. (FLU) once a day for 3 weeks after CUMS

Medial prefrontal cortex Western blot ↓GluN2B protein after CUMS
↑GluN2B protein after CUMS+ YY-21
↑GluN2B protein after CUMS+ FLU
Guo et al. [150]
GluN2A-B Sprague Dawley male rats
  • Chronic mild stress—8 weeks

(CMS)
Amygdala Western blot ↑GluN2A and GluN2B protein after CMS Zhou et al. [151]
GluN2A-B Dark Agouti male rats
  • Venlafaxine (VLX) 40 mg/kg s.c. (osmotic minipumps) each day for 21 days

Frontal cortex qPCR Grin2A and Grin2B mRNA after VLX Tamási et al. [152]
GluN2B Sprague Dawley male rats
  • Ketamine (KET) 10 mg/kg i.v. 24h before analysis

Hippocampus (HP)
Nucleus accumbens (NAc)
Amygdala (AMY)
Western blot ↓GluN2B protein after KET in HP
↑GluN2B protein after KET in NAc
↑GluN2B protein after KET in AMY
Piva et al. [153]
AMPA receptor complex
GluA1 Sprague Dawley male rats
  • CUMS—35 days

  • Ifenprodil 3 mg/kg i,p. (IFE) on day 37 (2 days after finish CUMS)

Hippocampus (HP)
Medial prefrontal cortex (mPFC)
Western blot ↓GluA1 protein after CUMS and ↑GluA1 protein after CUMS+ IFE in HP
↓GluA1 protein after CUMS and ↑GluA1 protein after CUMS+ IFE in mPFC
Yao et al. [154]
GluA1 Sprague Dawley
male rats
  • NVP-AAM07 10 mg/kg i.p.

Medial prefrontal cortex Western blot ↑GluA1 protein after NVP-AAM077 (only 30 min after administration) Gordillo-Salas et al. [155]
GluA1 Sprague Dawley male rats
  • CUS—28 days

  • Ifenprodil 3.0 mg/kg i,p. (IFE) 30 min before analysis

Medial prefrontal cortex Western blot ↓GluA1 protein after CUS
↑GluA1 protein after CUS+IFE
Li et al. [145]
GluA1
pS831-GluA1
pS845-GluA1
Sprague Dawley male rats
  • Olfactory bulbectomy (OB)

  • Sham-operated rats (Sham)

  • Magnesium hydroaspartate 15 mg/kg i.p. (calculated as magnesium ions; Mg15) once daily for 14 days

Prefrontal cortex (PFC)
Hippocampus (HP)
Amygdala (AMY)
Western blot ↔GluA1, pS831-GluA1, pS845-GluA1
proteins after OB in PFC vs. Sham
↔GluA1,↑pS831-GluA1 and pS845-GluA1 protein
after OB+ Mg15 in PFC vs. OB
↔GluA1, pS831-GluA1 and ↑pS845-GluA1 protein after OB in HP vs. Sham
↔GluA1, pS831-GluA1 and ↓pS845-GluA1 protein after OB+ Mg15 in HP vs. OB
↔GluA1, pS831-GluA1 and pS845-GluA1 protein after OB in AMY vs. Sham
↔GluA1, pS831-GluA1 and pS845-GluA1
protein after OB+ Mg15 in AMY vs. OB
Pochwat et al. [147]
GluA1
pS831-GluA1
pS845-GluA1
GluA2
Sprague Dawley male rats
  • CRS—14 days

  • Fasudil

10 mg/kg i.p. (FAS) for 18 days from the 5th day of CRS
Hippocampus
(whole tissue lysate)
Hippocampus
(synaptoneurosomes)
Western blot ↓GluA1 and
↔pS831-GluA1, pS845-GluA1, GluA2 protein level after CRS
↔GluA1, pS831-GluA1, pS845-GluA1, GluA2 protein after CRS+ FAS
↔GluA1, pS831-GluA1, pS845-GluA1, GluA2 protein after CRS
↔GluA1, pS845-GluA1, GluA2 and ↓pS831-GluA1
proteins after CRS+ FAS
Román-Albasini et al. [148]
GluA3 Dark Agouti male rats
  • Venlafaxine 40 mg/kg s.c. (osmotic minipumps) (VLX) for 21 days

Frontal cortex qPCR Gria3 mRNA after VLX Tamási et al. [152]
GluA1 Sprague Dawley male rats
  • CUMS—28 days

  • S-Ketamine 20 mg/kg i,p. (S-KET) once a day for 7 days

  • NSC23766 50 μg i.c.v once a day for 7 days

Hippocampus Western blot ↓GluA1 protein after CUMS
↑GluA1 protein after CUMS+S-KET
↔GluA1 protein after CUMS+ NSC23766 + S-KET
↔GluA1 protein after CUMS + NSC23766
Zhu et al. [156]
GluA1 Sprague Dawley
rats
  • Conditioned stimulus; white noise of 95 dB + unconditioned stimulus (CS-US); foot-shock 0.6 mA: 3/6/10 CS-US pairings)

  • Ketamine 10 mg/kg i,p. (KET) 24 h before analysis

  • Fluoxetine 10 mg/kg i,p. (FLU) for 28 days

Amygdala (AMY)
Prefrontal cortex (PFC)
Western blot ↑GluA1 protein after 3 CS-US in AMY
↔GluA1 protein after 6 CS-US in AMY
↑GluA1 protein after 10 CS-US in AMY
↓GluA1 protein after 10 CS-US+ KET in AMY
↔GluA1 protein after 10 CS-US + FLU in AMY
↓GluA1 protein after 3 CS-US in PFC
↓GluA1 protein after 6 CS-US in PFC
↓GluA1 protein after 10 CS-US in PFC
↑GluA1 protein after 10 CS-US+ KET in PFC
↔GluA1 protein after 10 CS-US + FLU in PFC
Lee et al. [157]
GluA1 Sprague Dawley male rats
  • CUMS—28 days

  • 7,8-Dihydroxy-4-methylcoumarin 10 mg/kg i,p. (Dhmc) once a day 30 min before receiving stress from day 11 to 28 for 18 days

  • Venlafaxine 10 mg/kg i,p. (VLX) once a day 30 min before receiving stress from day 11 to 28 for 18 days

Hippocampus Western blot ↓GluA1 protein after CUMS
↑GluA1 protein after CUMS+ VLX
↑GluA1 protein after CUMS+ Dhmc
Yang et al. [158]
GluA1
pS845-GluA1
Sprague Dawley male rats
  • CUMS—28 days

  • YY-21 10 mg/kg i.g. once a day for 3 weeks after CUMS

  • Fluoxetine 10 mg/kg i,p. (FLU) once a day for 3 weeks after CUMS

Medial prefrontal cortex Western blot ↔GluA1 and ↓pS845-GluA1 proteins after CUMS
↔GluA1 and ↑pS845-GluA1 proteins after CUMS+ YY-21
↔GluA1 and ↑pS845-GluA1 proteins after CUMS+ FLU
Guo et al. [150]
GluA1 Sprague Dawley male rats
  • Zinc hydroaspartate 5 mg/kg i,p. (Zn) 30 min, 3 h and 24 h before decapitation

Prefrontal cortex Western blot ↔GluA1 protein 30 min after Zn5 treatment
↑GluA1 protein 3 h after Zn5 treatment
↑GluA1 protein 24h after Zn treatment
Szewczyk et al. [159]
GluA1
pS845-GluA1
Sprague Dawley male and female rats
  • Ketamine 10 mg/kg i,p. (KET) before analysis

  • Memantine 10 mg/kg i,p. (MEM) before analysis

Hippocampus Western blot ↑GluA1 and pS845-GluA1 protein after KET
↔GluA1 and
↑pS845-GluA1 protein after MEM
Zhang et al. [160]
GluA1 Sprague Dawley male rats
  • CUS—21 days

Hypothalamic paraventricular nucleus (hPVN)
Hypothalamus (HY)
Western blot
qPCR
↑ GluA1 protein after CUS in hPVN
↑GluA1 protein and ↑Gria1 mRNA after CUS in HY
Li et al. [161]
GluA1-2 Sprague Dawley male rats
  • CUMS—35 days

  • sodium hydrosulfide 11.2 mg/kg i.p. (NaHS) before behavioral test

Hippocampus Western blot ↓GluA1 and GluA2 protein after CUMS
↑GluA1 protein after CUMS+ NaHS
↑GluA2 protein after CUMS+ NaHS
Hou et al. [162]
GluA1 Sprague Dawley male rats
  • Ketamine 10 mg/kg i.v. (KET) 24h before sacrifice

Hippocampus (HP)
Nucleus accumbens (NAc)
Amygdala (AMY)
Western blot ↓GluA1 protein after KET in HP
↓GluA1 protein after KET in NAc
↔GluA1 protein after KET in AMY
Piva et al. [153]
Metabotropic glutamate receptor 5
mGluR5 Sprague Dawley male rats
  • CUMS—42 days

  • Saikosaponin D: high-dose 1.5 mg/kg/d p.o. (SSDH); low-dose 0.75 mg/kg/d p.o. (SSDL) for 3 weeks

  • Fluoxetine 2.0 mg/kg/d p.o. (FLU) for 3 weeks

Hippocampus Western blot
Immunohistochemistry
qPCR
↓mGluR5 protein after CUMS
↑mGluR5 protein after CUMS+ FLU
↑mGluR5 protein after CUMS+ SSDH
↑mGluR5 protein after CUMS+ SSDL
↓mGluR5 protein after CUMS
↑mGluR5 protein after CUMS+ FLU
↑mGluR5 protein after CUMS+ SSDH
↑mGluR5 protein after CUMS+ SSDL
Grm5 mRNA after CUMS
Grm5mRNA after CUMS+ FLU
Grm5 mRNA after CUMS+ SSDH
Grm5 mRNA after CUMS+ SDDL
Liu et al. [163]
mGluR5 Sprague Dawley male rats
  • Ketamine 10 mg/kg i.v. (KET) 24h before sacrifice

Hippocampus (HP)
Nucleus accumbens (NAc)
Amygdala (AMY)
Western blot ↓mGluR5 protein after KET in HP
↓mGluR5 protein after KET in NAc
↑mGluR5 protein after KET in AMY
Piva et al. [153]

Abbreviations: YY-21—novel furostan skeleton secondary timosaponin, was obtained from timosaponin B-III via hydrolysis with hydrochloric acid; NVP-AAM07—[(S)-[[(1S)-1-(4-bromophenyl)ethyl]amino]-(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]phosphonic acid; preferring GluN2A subunit antagonist; NSC23766—(N6-[2-(4-Diethylamino-1-methyl-butylamino)-6-methyl-pyrimidin-4-yl]-2-methyl-quinoline-4,6-diamine); Rac1 inhibitor; qPCR—quantitative polymerase chain reaction.