The role of reactive oxygen species in methamphetamine self-administration and dopamine release in the nucleus accumbens.

Abstract:

:Methamphetamine (METH) markedly increases dopamine (DA) release in the mesolimbic DA system, which plays an important role in mediating the reinforcing effects of METH. METH-induced DA release results in the formation of reactive oxygen species (ROS), leading to oxidative damage. We have recently reported that ROS are implicated in behavior changes and DA release in the nucleus accumbens (NAc) following cocaine administration. The aim of this study was to evaluate the involvement of ROS in METH-induced locomotor activity, self-administration and enhancement of DA release in the NAc. Systemic administration of a non-specific ROS scavenger, N-tert-butyl-α-phenylnitrone (PBN; 0, 50 and 75 mg/kg, IP) or a superoxide-selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL; 0, 50 and 100 mg/kg, IP), attenuated METH-induced locomotor activity without affecting generalized behavior in METH-naïve rats. PBN and TEMPOL significantly attenuated METH self-administration without affecting food intake. Increased oxidative stress was found in neurons, but not astrocytes, microglia or oligodendrocytes, in the NAc of METH self-administering rats. In addition, TEMPOL significantly decreased METH enhancement of DA release in the NAc. Taken together, these results suggest that enhancement of ROS in the NAc contributes to the reinforcing effect of METH.

journal_name

Addict Biol

journal_title

Addiction biology

authors

Jang EY,Yang CH,Hedges DM,Kim SP,Lee JY,Ekins TG,Garcia BT,Kim HY,Nelson AC,Kim NJ,Steffensen SC

doi

10.1111/adb.12419

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

1304-1315

issue

5

eissn

1355-6215

issn

1369-1600

journal_volume

22

pub_type

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