Table 2. Changes in the NMDA receptor subunits and scaffolding proteins after withdrawal from noncontingent and contingent cocaine administration in rodents.
| Behavioural Model | Species | GLUN1 | GLUN2A | GLUN2B | GLUN3 | Refs. | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NONCONTINGENT COCAINE ADMINISTRATION | ||||||||||||||||
| 24 h, 72 h and 14 days of withdrawal from repeated cocaine injections (15 mg/kg; once a day; 7 days; i.p.) |
Sprague Dawley rats | VTA- ↑ (72 h and 14 days) | No data. |
CA1, CA3, or dentate gyrus of hippocampus- ϕ dorsolateral neostriatum- ↑ (14 days) medial frontal cortex- ↑ (24 h, 72 h and 14 days) nucleus accumbens shell- ↓ (24 h), ↑ (14 days) nucleus accumbens core- ↑ (14 days) lateral frontal cortex- ↑ (72 h and 14 days) parietal cortex- ↑ (72 h and 14 days) |
No data. | [34] | ||||||||||
| 24 h, 7 days of withdrawal from repeated cocaine injections (20 mg/kg; once a day; 14 days; i.p.) |
Sprague Dawley rats |
mRNA: cingulate cortex- ↓(24 h) parietal cortex- ↓(24 h) temporal cortex- ϕ CA1- ϕ CA2-3- ϕ striatum- ↓(24 h) dentate gyrus- ↑(24 h) thalamus- ϕ cerebellum- ϕ nucleus accumbens- ↓(24 h) globus pallidus- ↓(24 h) subiculum- ϕ entorhinal cortex- ↓(24 h) substantia nigra- ϕ |
mRNA: cingulate cortex- ϕ parietal cortex- ϕ temporal cortex- ϕ CA1- ϕ CA2-3- ϕ striatum- ϕ dentate gyrus- ϕ thalamus- ϕ cerebellum- ϕ nucleus accumbens- ϕ globus pallidus- ϕ subiculum- ϕ entorhinal cortex- ϕ substantia nigra- ϕ |
mRNA: cingulate cortex- ϕ parietal cortex- ↓(24 h) temporal cortex- ϕ CA1- ϕ CA2-3- ϕ striatum- ↓(24 h) dentate gyrus- ϕ thalamus- ϕ cerebellum- ϕ nucleus accumbens- ϕ globus pallidus- ϕ subiculum- ϕ entorhinal cortex- ϕ substantia nigra- ϕ GLUN2C: cerebellum- ↓(7d) No changes in other structures. |
No data. | [24] | ||||||||||
| 3 weeks of withdrawal from repeated cocaine injections (30 mg/kg; once a day; 7 days; i.p.) |
Sprague Dawley rats | No data. | prefrontal cortex- ↑ hippocampus- ↑ nucleus accumbens shell- ↓ nucleus accumbens core- ϕ dorsal striatum- ↑ |
prefrontal cortex- ↑ hippocampus- ϕ nucleus accumbens shell- ↓ nucleus accumbens core- ϕ dorsal striatum- ϕ |
No data. | [45] | ||||||||||
| 3 weeks of withdrawal from repeated cocaine injections (30 mg/kg; once a day; 7 days; i.p.) |
B6 mice | No data. | prefrontal cortex- ϕ hippocampus- ↑ nucleus accumbens shell- ϕ nucleus accumbens core- ϕ dorsal striatum- ↑ |
prefrontal cortex- ϕ hippocampus- ϕ nucleus accumbens shell- ϕ nucleus accumbens core- ϕ dorsal striatum- ϕ |
No data. | [45] | ||||||||||
| 15 days of withdrawal from repeated cocaine injections (15 mg/kg; once a day; 8 days; i.p.) |
Sprague Dawley rats | No data. | No data. | nucleus accumbens- ϕ dorsal striatum- ϕ |
No data. | [42] | ||||||||||
| Behavioural Model | Species | GLUN1 | GLUN2A | GLUN2B | GLUN3 | Refs. | ||||||||||
| NONCONTINGENT COCAINE ADMINISTRATION | ||||||||||||||||
| 1 day or 21 days after cocaine sensitization (15 mg/kg; 5 days; i.p.)) | Sabra rats | nucleus accumbens- ↓ (1 d- synaptosomal membranes); ↑ (1 d -light membrane fraction) nucleus accumbens- ↑ (21 d- synaptosomal membranes and homogenate) hippocampus- ϕ |
nucleus accumbens- ↓ (1 d- synaptosomal membranes); ↑ (1 d -light membrane fraction) nucleus accumbens- ↑ (21 d- synaptosomal membranes and homogenate) hippocampus- ϕ |
nucleus accumbens- ↓ (1 d- synaptosomal membranes); ↑ (1 d -light membrane fraction) nucleus accumbens- ↑ (21 d- synaptosomal membranes and homogenate) hippocampus- ϕ |
No data. | [43] | ||||||||||
| 30 h of withdrawal from repeated cocaine injections (20 mg/kg; once a day; 7 days; i.p.) |
Sprague Dawley rats | ventral hippocampus- ϕ | ventral hippocampus- ϕ |
ventral hippocampus- ϕ | No data. | [44] | ||||||||||
| 0, 1, 5, 10 days of withdrawal from non-contingent cocaine injections (1 mg/kg/inf.; 3 weeks; i.v..) |
Lewis rats |
mRNA: medial prefrontal cortex- ↑ (1 d, 5 d) caudate putamen- ↑ (1 d, 5 d) nucleus accumbens- ↑ (5 d) olfactory tubercle- ↑ (1 d, 5 d) piriform cortex- ↑ (1 d, 5 d, 10 d) |
No data. | No data. | No data. | [41] | ||||||||||
| CONTINGENT COCAINE ADMINISTRATION | ||||||||||||||||
| 0, 1, 5, 10 days of extinction from contingent cocaine self‐administration (1 mg/kg/inf.; 3 weeks; i.v.) |
Lewis rats |
mRNA: medial prefrontal cortex- ↑ (0 d, 1 d); ↓ (10 d) caudate putamen- ↑ (0 d, 1 d- cont); ↓ (5 d, 10 d- cont) nucleus accumbens- ↑ (0 d- cont); ↓ (5 d, 10 d- cont) olfactory tubercle- ↑ (0 d, 1 d- cont) piriform cortex- ↑ (0 d, 1 d- cont) |
No data. | No data. | No data. | [41] | ||||||||||
| 1, 30, 90 days of withdrawal from cocaine self‐administration (1 mg/kg/inf.; 10 days; i.v.) | Long-Evans rats | VTA- ↑ (1 d, 30 d, 90 d) nucleus accumbens- ↑ (1 d, 90 d) |
No data. | No data. | No data. | [54] | ||||||||||
| 7 days of withdrawal from cocaine self‐administration (1 mg/kg/inf.; 14 days; i.v.) | Sprague Dawley rats | nucleus accumbens core- ↓ nucleus accumbens shell- ϕ |
No data. | No data. | No data. | [58] | ||||||||||
| 14 days of withdrawal from cocaine binge access - cocaine self-administration (0.5 mg/kg/infusion; 8-h/day; 14 days) - cocaine binge- multiple 3h self-administration; 1h time outs; 6 days) |
Sprague Dawley rats | VTA- ϕ substantia nigra- ϕ nucleus accumbens- ϕ striatum- ↑ prefrontal cortex- ϕ |
No data. | VTA- ϕ substantia nigra- ϕ nucleus accumbens- ϕ striatum- ↑ prefrontal cortex- ↑ |
3A: nucleus accumbens- ϕ striatum- ϕ prefrontal cortex- ↓ 3B: nucleus accumbens- ϕ striatum- ↑ prefrontal cortex- ϕ |
[49] | ||||||||||
| Behavioural Model | Species | GLUN1 | GLUN2A | GLUN2B | GLUN3 | Refs. | ||||||||||
| CONTINGENT COCAINE ADMINISTRATION | ||||||||||||||||
| 10-14 days of abstinence from cocaine self-administration (1 mg/kg/infusion; 6-h session; 14 days) Home cage SA box Extinction |
Sprague-Dawley rats |
Home cage: nucleus accumbens shell- ϕ nucleus accumbens core- ϕ dorsolateral striatum- ↓ (total) SA box: nucleus accumbens shell- ϕ nucleus accumbens core- ϕ dorsolateral striatum- ↓ (total) Extinction: nucleus accumbens shell- ↓ (synaptosomal) nucleus accumbens core- ϕ dorsolateral striatum- ↑ (total and synaptosomal) |
No data. | No data. | No data. | [57] | ||||||||||
|
SCAFFOLDING PROTEIN: PSD95: Home cage: nucleus accumbens shell- ϕ nucleus accumbens core- ϕ dorsolateral striatum- ϕ SA box: nucleus accumbens shell- ϕ nucleus accumbens core- ϕ dorsolateral striatum- ϕ Extinction: nucleus accumbens shell- ↓ (synaptosomal) nucleus accumbens core- ↑ (total) dorsolateral striatum- ϕ | ||||||||||||||||
| 1, 14, 60 days of withdrawal from cocaine self-administration (0.25 mg/kg/infusion; 1-h session; 7 days) and - brief access (1h; 10 days) -extended access (6h; 10 days) |
Sprague-Dawley rats | No data. | medial prefrontal cortex- ↑ (extended; 60 d) nucleus accumbens core- ϕ nucleus accumbens shell- ϕ VTA- ϕ |
medial prefrontal cortex- ↑ (extended; 14 d) nucleus accumbens core- ϕ nucleus accumbens shell- ϕ VTA- ϕ |
No data. | [60] | ||||||||||
| 45 days of withdrawal from cocaine self-administration (0.5 mg/kg/infusion; 6-h/day; 10 days) |
Sprague Dawley rats | nucleus accumbens- ϕ | nucleus accumbens- ϕ | nucleus accumbens- ϕ | No data. | [53] | ||||||||||
| 1 day of withdrawal from cocaine self-administration (0.25 mg/kg/infusion; 2-h/day; 14 days) |
Sprague Dawley rats | nucleus accumbens shell- ϕ | nucleus accumbens shell- ↑ | nucleus accumbens shell- ↑ | No data. | [56] | ||||||||||
| 1 day of extinction from cocaine self-administration (0.5 mg/kg/infusion; 2-h/day; 14 days) |
Wistar rats | hippocampus- ϕ (homogenate); ϕ (post-synaptic density) | hippocampus- ϕ (homogenate); ϕ (post-synaptic density) | hippocampus- ϕ (homogenate); ϕ (post-synaptic density) | No data. | [39] | ||||||||||
|
SCAFFOLDING PROTEINS: SAP102: hippocampus- ϕ (homogenate); ϕ (post-synaptic density) SAP97: hippocampus- ϕ (homogenate); ϕ (post-synaptic density) PSD95: hippocampus- ϕ (homogenate); ϕ (post-synaptic density) | ||||||||||||||||
| 10 days of extinction from cocaine self-administration (0.5 mg/kg/infusion; 2-h/day; 14 days) |
Wistar rats | hippocampus- ϕ (homogenate); ϕ (post-synaptic density) | hippocampus- ϕ (homogenate); ϕ (post-synaptic density) | hippocampus- ϕ (homogenate); ϕ (post-synaptic density) | No data. | [39] | ||||||||||
|
SCAFFOLDING PROTEINS: SAP102: hippocampus- ϕ (homogenate); ϕ (post-synaptic density) SAP97: hippocampus- ↓YC (homogenate); ↓YC (post-synaptic density) PSD95: hippocampus- ϕ (homogenate); ϕ (post-synaptic density) | ||||||||||||||||
| Behavioural Model | Species | GLUN1 | GLUN2A | GLUN2B | GLUN3 | Refs. | ||||||||||
| CONTINGENT COCAINE ADMINISTRATION | ||||||||||||||||
| 13 days of abstinence from cocaine self-administration (0.25 mg/kg/infusion; 1.5 h/day; 4 days) Home cage Extinction |
Long-Evans rats | No data. | ventromedial prefrontal cortex- ϕ nucleus accumbens- ↑ home cage; ↑ extinction |
ventromedial prefrontal cortex- ϕ nucleus accumbens- ↑ home cage |
No data. | [55] | ||||||||||
| 10 days of extinction from cocaine self-administration (0.5 mg/kg/infusion; 2-h/day; 14 days) |
Wistar rats | prefrontal cortex- ϕ hippocampus- ↑SA; ↑YC dorsal striatum- ϕ nucleus accumbens- ↑SA; ↑YC |
prefrontal cortex- ↑SA; ↑YC hippocampus- ↑SA dorsal striatum- ϕ nucleus accumbens- ϕ |
prefrontal cortex- ϕ hippocampus- ↑SA dorsal striatum- ϕ nucleus accumbens- ϕ |
No data. | [3] | ||||||||||
| 3, 30 days of withdrawal from cocaine self-administration (0.25 mg/kg/infusion; 6-h/day; 10 days) | Sprague Dawley rats | No data. | dorsomedial prefrontal cortex- ϕ ventromedial prefrontal cortex- ϕ |
dorsomedial prefrontal cortex- ↑ (3, 30 d) ventromedial prefrontal cortex- ϕ |
No data. | [59] | ||||||||||
Abbreviations: ϕ- no changes; ↑- increase; ↓- decrease; h- hour; i.p.- intraperitoneal; i.v.- intravenous; SA- self-administered group; YC- “yoked” cocaine group; VTA- ventral tegmental area.