TABLE 3.
Effects of opioids on the ECM.
| Treatment | Species | Brain area | Preharvest interval | ECM effect | Manipulation | Behavioral effect | References |
| Acute opioid exposure | |||||||
| Morphine and EM-2 incubation in vitro | MCF-7 breast cancer cell line | NA | 3–72 h in culture | Concentration-gradient ↓ of Mmp2 and Mmp9 by morphine and EM-2 | NA | NA | Gach et al., 2011 |
| Heroin IVSA cued RST | Rat | NAc | 0 min | Increased MMP-9 puncta around D1R MSNs | MMP-2 and MMP-9 inhibitors | MMP-9 inhibitors decrease cued reinstatement | Chioma et al., 2021 |
| Morphine incubation in vitro | Human brain microvascular endothelial cells | NA | 24 h | ↓ MMP-2, LAMA-4 | NA | NA | Vujic et al., 2022 |
| Chronic opioid exposure | |||||||
| Heroin IVSA, EXT and RST |
Rat | mPFC, NAc, striatum | 21 days (EXT) | EXT: ↓ TNR and BCAN in NAc, ↓ 145 kDa BCAN in mPFC | i.c.v. FN439 injection | Decreased cue-induced heroin RST | Van den Oever et al., 2010 |
| 0 min (RST) | RST: ↓ TNR in NAc | ||||||
| Heroin IVSA RST | Rat | NAc | 15 min after RST | ↑ MMP-9 by cue exposure | NA | NA | Smith et al., 2014 |
| Escalating morphine and naloxone mediated withdrawal |
Rat | Spinal cord (laminae I-VII) | 48 h | Significant increase of MMP-9 in morphine treated animals | Intrathecal MMP-9 inhibition | ↓ Morphine withdrawal | Liu et al., 2010 |
| No effect on pain-threshold or morphine-induced analgesia | |||||||
| Heroin IVSA forced abstinence |
Rat | IL-PFC and vOFC | 1 day | 1 day: ↑ PNNs in IL and OFC | NA | NA | Roura-Martinez et al., 2020 |
| 30 d | 30 days: No PNN changes compared to controls | ||||||
| Opioid use disorder | Human | DL-PFC and NAc | Postmortem | ↑ Differentially expressed transcripts related to CS-GAG biosynthesis in DL-PFC, NAc | NA | NA | Seney et al., 2021 |
| Opioid use disorder | Human | Midbrain | Postmortem (overdose) | ↑ IL-4 in opioid overdoses | NA | NA | Wei et al., 2023 |
Acute (top) and chronic (bottom) effects of opioids on ECM molecules. Preharvest interval denotes the time between the most recent drug exposure and euthanasia. CPP, conditioned place preference; IVSA, intravenous drug self-administration; NAc, nucleus accumbens; HPC, hippocampus; PFC, prefrontal cortex; IL, infralimbic; PL, prelimbic; VTA, ventral tegmental area; LH, lateral hypothalamus; OFC, orbitofrontal cortex; MMP, matrix metalloproteinase; chABC, chondroitinase ABC; PNN, perineuronal net; TNR, tenascin-R; LAMA, laminin; tPA, tissue plasminogen activator; HS, heparan sulfate; D1R/D2R, dopamine 1 and 2 receptors; MSN, medium spiny neuron; IL, interleukin.