Matrix Metalloproteinases Contribute to Neuronal Dysfunction in Animal Models of Drug Dependence, Alzheimer's Disease, and Epilepsy

Table 4

Summary of changes in addictive behaviors and dopamine release in response to inhibition of the MMP/TIMP system.

Test	Drug	TIMP-2-AS	Doxycycline, FN-439; (MMP inhibitor)	MMP-2^(−/−)	MMP-9^(−/−)	References
Hyperlocomotion; (single treatment)	Methamphetamine	±	±	±	±	[32, 33]
Locomotor sensitization (repeated treatment)	Methamphetamine	⇑	⇓	⇓	⇓	[32, 33]
Conditioned place preference (rewarding effect, and drug-associated memory)	Methamphetamine	N.D.	⇓	⇓	⇓	[32, 33]
	Cocaine	N.D.	⇓	N.D.	N.D.	[37]
Self-administration	Alcohol	N.D.	⇓	N.D.	N.D.	[41]
Dopamine release	Methamphetamine	⇑	⇓	⇓	⇓	[32, 33]

±: no change; ⇑: significant increase versus control mice; ⇓: significant decrease versus control mice; N.D.: not determined.
TIMP-2-AS: antisense TIMP-2 oligonucleotides.