Table 1. Relevance of HINT1 proteins and σ1Rs in GPCR-NMDAR cross-regulation.

HINT1−/− mice	References
Impaired association of MOR with the NMDAR NR1 subunit	[49]
Enhanced morphine antinociception	[27, 42]
Enhanced and NMDAR-independent antinociceptive tolerance	[27, 49]
Heterologous tolerance	[49]
NMDA does not antagonize morphine antinociception	[49]
Cannabinoids do not reduce NMDAR activity	[25, 17]
HINT1 restores CB1 protection against excitotoxicity	[17]
Impaired association of CB1 with NMDAR NR1 subunit	[25]
Anti-depressant and anxiolytic-like behaviors	[39]
Dysregulated postsynaptic dopaminergic transmission	[38]
The HINT1 protein and neurological disorders
HINT1 gene is a candidate for schizophrenia	[29, 30, 31]
Association of the HINT1 gene with nicotine dependence	[36, 37]
σ1R−/− mice	References
Impaired association of MOR with the NMDAR NR1 subunit	[28]
Enhanced morphine antinociception	[28, 71, 72]
Nearly absent allodynia	[56, 90]
Enhanced and NMDAR-independent antinociceptive tolerance	[28]
Heterologous tolerance
NMDA does not antagonize morphine antinociception
The σ1R restores MOR-NMDAR cross-regulation
Cannabinoids do not reduce NMDAR activity	[8]
NMDAR activity does not recruit CB1 control
Impaired association of CB1 with the NMDAR NR1 subunit
The σ1R and neurological disorders
The σ1R gene is a candidate for schizophrenia	[32, 33, 34, 35]
σ1R ligands are antidepressants and anxiolytics	[40, 41]