TABLE 1.
1a. Schizophrenia-related rat models | |||||||
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Model | NAC application | Cognitive domain | Negative domain | Other changes | References | ||
BSO | Chronic p.o. 10 and 30 mg/kg/d P68–89 | ↑OM (NOR) | ↑ Social interaction | ↑ Efficacy of aripiprazole ↑ BDNF |
Rogóż et al., 2022 | ||
SIR | Chronic i.p. 150 mg/kg/d P63–77 | ↑OM (NOR) | ↑Social interaction | ↑Rearing, ↑ PPI ↑ Clozapine efficacy ↓ proInflam. cytokines ↓ KYN/KYN-A ↓ DA (STR); ↑DA (FC) |
Möller et al., 2013 | ||
NVHL | Chronic 0.9 g/l d-water P5–50 | – | – | ↑ PVI and PNNs ↓ Oxidative stress ↑MMN, PPI |
Cabungcal et al., 2014 | ||
MIA + MA | Chronic s.c. 150 mg/kg/d P51–64 | ↑OM (NOR) | ↑Social interaction | ↑ PPI ↑ NA (FC, STR) ↓ Oxidative stress |
Swanepoel et al., 2018 | ||
Poly-I:C and PUS | Chronic i.p. 220 mg/kg/d P30–59 | ↑WM (alternation) | ↑Social interaction | ↑ PPI (♀ only) ↓ LMA ↓ Oxidative stress ↑ PVI (♀ only) |
Monte et al., 2020 | ||
APO-SUS | Chronic, 0.9 g/l d-water P5–40, 2 g/l P40–90 | ↑Cognitive flexibility |
– | ↓ Oxidative stress ↑ myelination |
Maas et al., 2021 | ||
MAM | Chronic 0.9 g/l d-water P11–25 | – | – | ↑ PVI and PNNs ↓ Oxidative stress |
Zhu et al., 2021 | ||
MAM | Chronic i.p. 250 mg/kg/d P75–90 | – | ↑Social interaction | ↓ MK801-induced LMA |
Lopes-Rocha et al., 2022 | ||
MAM | Acute i.p. 150–500 mg/kg | – | ↑Social interaction | ↓ MK801-induced LMA | Lopes-Rocha et al., 2022 | ||
PCP | Acute i.p. 90 mg/kg | ↑WM (alternation) | ↑Social interaction | ↓ Glutamate release | Baker et al., 2008 | ||
MA | Acute i.p. 100 and 300 mg/kg | – | – | ↓ MA-induced LMA | Fukami et al., 2004 | ||
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1b. Schizophrenia-related mouse models | |||||||
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Model | NAC application | Cognitive domain | Negative domain | Other changes | References | ||
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G72Tg | Chronic 1 g/l d-water 3–8 weeks | ↑SLTM (MWM) | – | – | Otte et al., 2011 | ||
ketamine | Chronic s.c. 10 mg/kg P5–21; 1 g/l d-water from P22; or P35–56 | ↑WM (alternation) ↑Cognitive flexibility ↑OM (NOR) |
↑Social interaction ↑ Social novelty pref. |
↑ PPI ↑ PVI ↓ Oxidative stress |
Phensy et al., 2017a,b | ||
Gclm KO | Chronic 0.9 g/l d-water P20–35 | – | – | ↓ MMP9/RAGE ↑ PVI and PNNs |
Dwir et al., 2021 | ||
-/KYN | 7 days i.p. 100 mg/kg/d | ↑SLTM (food location) | – | ↓ KYN/KYN-A ↓ Oxidative stress |
Blanco Ayala et al., 2021 | ||
Grm5 KO | Acute i.p. 50 and 100 mg/kg | – | – | ↑ PPI | Chen et al., 2010 | ||
Amph | Acute i.p. 60 mg/kg | – | – | ↓ Amphetamine sensitization-induced LMA | Herrmann et al., 2017 | ||
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1c. Models related to other brain disorders | |||||||
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Primary disorder | Species | Model | NAC application | Cognitive domain | Negative domain | Other changes | References |
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MDD | Rat | CLI | Chronic i.p. 100 mg/kg/d, P76–89 | ↑WM (alternation) | ↓Depression ↓Anhedonia (SPT) |
↑ HC volume ↑ HC monoamines ↓ Anxiety |
Chakraborty et al., 2020b |
Rat | CLI | Chronic i.p. 100 mg/kg/d, P76–89 | – | ↓Anhedonia (SPT) |
↓ Anxiety ↓ Adrenal and spleen volume ↓ Corticosterone |
Chakraborty et al., 2020a | |
Rat | OBX | 10 days i.p. 50 and 100 mg/kg/d | – | ↓Depression (FST) | ↑ HC and FC SOD activity |
Smaga et al., 2012 | |
Rat | CUMS | 1 week p.o 50 and 100 mg/kg/d | – | ↓Depression (FST) ↓Anhedonia (SPT) |
↑ HC serotonin ↓ proInflam cytokines |
Fernandes and Gupta, 2019 | |
Rat | Alcohol abstinence | 3 days i.p.50 and 100 mg/kg/d | – | ↓Depression (FST, TST) | ↓ GRIN2A/B ↑ HC serotonin |
Yawalkar et al., 2018 | |
Rat | - | Acute i.p. 15–150 mg/kg | – | ↓Depression (FST) | – | Ferreira et al., 2008 | |
Rat | OBX | Acute i.p. 25–100 mg/kg | – | – | ↓ Cocaine-seeking | Frankowska et al., 2014 | |
Mouse | Repeated audible noise | Chronic p.o. 325 mg/kg/d for 30 days | – | ↓Depression (TST) ↓anhedonia (SPT) |
↓Anxiety ↑ Exploration ↓ Oxidative stress |
Mahmoodzadeh et al., 2021 | |
Mouse | – | Acute i.p. 25 mg/kg | – | ↓Depression (TST) | ↑Efficacy of imipramine and escitalopram | Costa-Campos et al., 2013 | |
OCD | Mouse | – | Acute i.p. 150 mg/kg | – | – | ↓Marble burying | Egashira et al., 2012 |
Aging | Mouse | – | Chronic 3 g/kg food, for 10 weeks | ↑SLTM (MWM) | – | – | Ikonne et al., 2019 |
AD | Mouse | ApoE4 | Chronica, 5 g/kg food | ↑WM (alternation) | – | ↓ Aggression | Shea, 2007 |
Mouse | SAMP8 | Chronic s.c. 100 mg/kg/d for 4 weeks | ↑ Conditioned avoidance | – | – | Farr et al., 2003 | |
HD | Mouse | R6/1 | Chronic i.p. 500 mg/kg/d for 8–12/17 weeks | – | ↓Depression (FST) | ↑ Motor function ↑ Mitochondrial function ↓ GluN2B ↑ Glutamate |
(Wright et al., 2015, 2016) |
Mouse | R6/1 | Acute i.p. 500 mg/kg | – | ↓Depression (FST) | – | Wright et al., 2016 | |
AE | Rat | WAG/Rij | Chronic p.o. 500 mg/kg/d for 30 days | ↑OM (NOR) | ↓Depression (FST) | Epilepsy worsens! ↑ mGluR2 |
Tallarico et al., 2022 |
aApplied in combination with ALCAR (acetyl-L-carnitine; 1 g/kg diet) and SAM (S-adenosyl methionine; 100 mg/kg diet). AD, Alzheimer’s disease; AE, absence epilepsy; Amph, repeated amphetamine application (amphetamine sensitization); APO-SUS, apomorphine-susceptible rat; BSO, L-buthionine-(S,R)-sulfoximine developmental model of SCZ; CLI, neonatal/juvenile clomipramine application model of depression; CUMS, chronic unpredictable mild stress model of depression; DA, dopamine; d-water, drinking water; FC, frontal cortex; FST, force-swim test; Gclm, glutamate-cysteine ligase modulatory subunit; HC, hippocampus; HD, Huntington’s Disease; KYN/KYN-A, kynurenine/kynurenic acid; LMA, locomotor activity; MA, methamphetamine developmental model of SCZ; MAM, methylazoxymethanol acetate developmental model of SCZ; MDD, major depressive disorder; MMP9/RAGE, matrix-metalloprotease 9/receptor for advanced glycation end-products; MIA, developmental LPS-based maternal immune activation model of SCZ; MMN, mismatch-negativity of the auditory evoked potential; MWM, Morris water-maze; NA, noradrenaline; NOR, novel-object recognition test; NVHL, neonatal ventral hippocampal lesion model of SCZ; OBX, bulbectomization model of depression; OCD, obsessive compulsive disorder; OM, short-term object memory; PCP, phencyclidine model of SCZ; PNNs, perineuronal-nets; Poly-I:C, polyinosinic:polycytidylic acid viral mimetic developmental model of SCZ; PPI, pre-pulse inhibition of the startle response; PUS, peripubertal unpredictable stress; PVI, parvalbumin-positive interneurons; SIR, social isolation rearing; SLTM, spatial long-term memory; SOD, superoxide dismutase (anti-oxidant mechanism); SPT, sucrose-preference test; TST, tail-suspension test; WM, working memory.