TABLE 2.

Effects of psychostimulants on the ECM.

Treatment	Species	Brain area	Preharvest interval	ECM effect	Manipulation	Behavioral effect	References
Acute psychostimulant exposure
Experimenter-administered cocaine	Mouse	NAc	30 min	↓β1-integrin	NA	NA	Wiggins et al., 2009
Cocaine IVSA	Mouse	NA	NA	NA	Heterozygous β3-integrin deficiency	↓ Cue-induced cocaine seeking	Garcia-Keller et al., 2019
				NA		↓ Enhancement of cue-induced cocaine seeking by MMP-9
Cocaine CPP	Rat	NAc	NA	NA	Intra-NAc lentivirus upregulation of uPA	↑ CPP	Bahi et al., 2008
		NA	NA	NA	Inhibition of uPA with doxycycline	↓ Enhancement of CPP
Nicotine conditioned place preference	Rat	HPC and PFC	3 h	↑ MMP-2 and MMP-9	NA	NA	Natarajan et al., 2013
Cocaine CPP and locomotor activity recordings	Mouse	NA	NA	NA	Heterozygous reelin deficiency	↑ Cocaine-induced hyperlocomotion	de Guglielmo et al., 2022
						No effect on CPP
Experimenter-administered meth	Mouse	NA	NA	NA	Heterozygous reelin deficiency	No effect on meth-induced hyperlocomotion	Hume et al., 2020
Single cocaine injection	Rat	IL and PL PFC	2 h or 24 h	2 h: ↓ PNNs not apposing PVB neurons	NA	NA	Slaker et al., 2018
Single cocaine injection	Mouse	Amygdala, NAc, putamen	30 min	↑ tPA activity in amygdala	Homozygous tPA KO	Cocaine induces anxiolysis in tPA KO mice	Maiya et al., 2009
Single cocaine injection	Rat	HPC, NAc	1 day	↑Sema3a in hippocampus	NA	NA	Bahi and Dreyer, 2005
				↓Sema3a in NAc
Chronic psychostimulant exposure
Cocaine use disorder	Human	HPC	Postmortem	↓ MMP-9 protein	NA	NA	Mash et al., 2007
				↑β1-laminin and β6-integrin mRNA
Experimenter-administered cocaine	Rat	IL and PL PFC	5 days: 2 h or 24 h	2 h: ↑ PNNs apposing PVB neurons 24 h: No effect	NA	NA	Slaker et al., 2018
Experimenter-administered cocaine (7 days)	Mouse	Deep cerebellar medial nucleus	24 h after last cocaine	↑ strong-type PNN labeling	NA	NA	Vazquez-Sanroman et al., 2015
Cocaine CPP	Rat	Cerebellum (lobule VIII of vermis)	8 cocaine pairings: 1.5 h after test (25.5 h after last cocaine)	NA	Intra-cerebellar chABC prior to CPP	No effect on CPP acquisition	Guarque-Chabrera et al., 2022
Cocaine CPP short-term memory (cue exposure)	Rat	Cerebellum, lobule VIII of vermis (LVIII)	6 days after last cocaine	NA	Intra-LVIII chABC prior to retest	↓ Cocaine short-term memory	Guarque-Chabrera et al., 2022
		Deep cerebellar nuclei (DCN)			Intra-DCN chABC prior to retest
Stable nicotine IVSA	Rat	VTA and OFC	45 min after last session	45 min: ↓ PNNs apposing PVB neurons in VTA, OFC	NA	NA	Vazquez-Sanroman et al., 2017
			72 h after last session	72 h:↓ PNNs apposing PVB neurons in VTA, no effect in OFC
Chronic (15 days) cocaine injections	Rat	HPC, NAc, VTA	24 h after last cocaine	↑ Sema mRNA in HPC, NAc, and VTA	NA	NA	Bahi and Dreyer, 2005
Cocaine RST from forced abstinence	Rat	HPC, VTA, NAc	24 h after last cocaine	↑ Sema3a in HPC	NA	NA	Bahi and Dreyer, 2005
				↓ Sema3a in NAc
Chronic (13 days) cocaine and meth injections	Mouse	LH	Unknown	↑ HS disaccharide and sulfation content	NA	NA	Chen et al., 2017
Chronic (7 days) cocaine injections	Mouse	NAc	3 weeks since last cocaine	↑β1-integrin	NA	NA	Wiggins et al., 2009
Cocaine CPP	Rat	PL PFC	24 h	↑ PNNs apposing c-Fos neurons	NA	NA	Slaker et al., 2015
Chronic (5 days) meth injections	Rat	PFC, NAc, striatum, and VTA	2 h	↑ Timp2 in PFC, NAc, and striatum	D1R and D2R antagonism	↓ Meth-induced Timp induction	Mizoguchi et al., 2007
Cocaine CPP RST	Rat	PFC and HPC	1, 3, 24 h	↑ MMP-9 and -2 in PFC at all timepoints, no changes in HPC	NA	NA	Brown et al., 2008
Cocaine CPP	Rat	PL PFC	24 h	↓ PNNs apposing c-Fos neurons in chABC animals	Intra-PL chABC before acquisition	↓ CPP	Slaker et al., 2015
Cocaine CPP RST	Rat	PL PFC	1 h	↓ PNNs apposing c-Fos neurons in chABC animals	Intra-PL chABC before memory reactivation	↓ CPP	Slaker et al., 2015
Cocaine EXT	Rat	PL PFC	∼14 days	No effect on PNNs apposing cFos neurons in chABC animals	Intra-PL chABC before extinction	No effect	Slaker et al., 2015
Cocaine IVSA RST	Rat	NAc	15 min after RST	↑ MMP-9 by cues for cocaine	NA	NA	Smith et al., 2014
Cocaine IVSA RST	Rat	NAc	15 min after RST	NA	FAK inhibitor	↓ Reinstatement of cocaine IVSA	Garcia-Keller et al., 2020
Meth cue exposure during abstinence	Rat	NAc	30 min after cued relapse	Increased MMP-2,9 by meth cues	NA	NA	Lewandowski et al., 2023
Cocaine CPP and IVSA	Rat	LH	NA	NA	Intra-LH chABC injection before behavior	↓ CPP and IVSA	Blacktop et al., 2017

Acute (top) and chronic (bottom) effects of cocaine, methamphetamine, and nicotine 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; RST, reinstatement; 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; PVB, parvalbumin; SEMA, semaphorin; TIMP, tissue inhibitor of metalloproteinase; tPA, tissue plasminogen activator; HS, heparan sulfate; D1R/D2R, dopamine 1 and 2 receptors, FAK; focal adhesion kinase.