Oxidative stress biomarkers in some rat brain structures and peripheral organs underwent cocaine

Abstract

Oxidative stress (OS) generates or intensifies cocaine-evoked toxicity in the brain and peripheral organs. The aim of this study was to examine superoxide dismutase (SOD) activity and lipid peroxidation [measured by malondialdehyde (MDA) levels] in rats during maintenance of cocaine self-administration and after withdrawal by a yoked-triad procedure. Our results indicate that repeated cocaine self-administration provoked an elevation of SOD activity in the hippocampus, frontal cortex, dorsal striatum, and liver. MDA levels were reduced in the brain, increased in the liver, kidney, and heart during maintenance of self-administration, and increased in the kidney in cocaine-yoked rats. In addition, following extinction training, we found enhanced MDA levels and SOD activity in the rat hippocampus, while changes in the activity of OS biomarkers in other brain structures and peripheral tissues were reminiscent of the changes seen during cocaine self-administration. These findings highlight the association between OS biomarkers in motivational processes related to voluntary cocaine intake in rats. OS participates in memory and learning impairments that could be involved in drug toxicity and addiction mechanisms. Therefore, further studies are necessary to address protective mechanisms against cocaine-induced brain and peripheral tissue damage.

Fig. 1

The mean number (±SEM) of responses in active and inactive levers for rats that acquired self-administration of cocaine at a dose of 0.5 mg/kg/injection and their yoked controls that received passive infusions of cocaine or saline. *p < 0.001 versus inactive lever. N = 6–8 rats/group

Fig. 2

SOD activity in brain structures during cocaine (coc) self-administration (SA) by yoked-triad procedure. Data shown as a % of control ± SEM; *p < 0.05, ***p < 0.0001 versus yoked saline (sal); ^# p < 0.05, ^### p < 0.001 versus yoked cocaine. In control (yoked saline) rats, the absolute SOD activity was 7.64 ± 0.28 U/mg protein in the hippocampus, 4.03 ± 0.39 U/mg protein in the frontal cortex and 6.32 ± 0.48 U/mg protein in the dorsal striatum. N = 6–8 rats/group

Fig. 3

MDA concentration in brain structures during cocaine (coc) self-administration (SA) by yoked-triad procedure. Data shown as a % of control ± SEM; *p < 0.05, **p < 0.01 versus yoked saline (sal); ^# p < 0.05 versus yoked cocaine. In control (yoked saline) group, the absolute MDA level was 173 ± 6.4 μM/g tissue in the hippocampus, 143 ± 7.3 μM/g tissue in the frontal cortex and 179.6 ± 12.5 μM/g tissue in the dorsal striatum. N = 6–8 rats/group

Fig. 4

SOD activity in peripheral organs during cocaine (coc) self-administration (SA) by yoked-triad procedure. Data are shown as mean ± SEM; ***p < 0.001 versus yoked saline (sal). In control (yoked saline) rats, the absolute SOD activity was 3.5 ± 0.09 U/mg protein in the liver, 7.3 ± 0.19 U/mg protein in kidney and 6.4 ± 0.52 U/mg protein in the heart. N = 6–8 rats/group

Fig. 5

MDA concentration in peripheral organs during cocaine (coc) self-administration (SA) by yoked-triad procedure. Data are shown as mean ± SEM; *p < 0.05, **p < 0.01, ***p < 0.001 versus yoked saline (sal); ^### p < 0.001 versus yoked cocaine (coc). In control (yoked saline) group, the absolute MDA level was 20.67 ± 1.4 μM/g tissue in the liver, 328.5 ± 13.42 μM/g tissue in kidney and 17.72 ± 1.6 μM/g tissue in the heart. N = 6–8 rats/group

Fig. 6

SOD activity in brain structures after cocaine (coc) self-administration (SA) and extinction training by yoked-triad procedure. Data shown as a % of control ± SEM; *p < 0.05, ***p < 0.001 versus yoked saline (sal); ^# p < 0.05, ^### p < 0.001 versus yoked cocaine. In control (yoked saline) rats, the absolute SOD activity was 6.3 ± 0.3 U/mg protein in the hippocampus, 3.92 ± 0.36 U/mg protein in the frontal cortex and 5.36 ± 0.62 U/mg protein in the dorsal striatum. N = 6–8 rats/group

Fig. 7

MDA concentration in brain structures after cocaine (coc) self-administration (SA) and extinction training by yoked-triad procedure. Data shown as a % of control ± SEM; *p < 0.05, **p < 0.01 versus yoked saline (sal). In control (yoked saline) group, the absolute MDA level was 182.4 ± 5.6 μM/g tissue in the hippocampus, 142 ± 7.8 μM/g tissue in the frontal cortex and 186 ± 11.9 μM/g tissue in the dorsal striatum. N = 6–8 rats/group

Fig. 8

SOD activity in peripheral organs after cocaine (coc) self-administration (SA) and extinction training by yoked-triad procedure. Data shown as a % of control ± SEM; *p < 0.05, ***p < 0.001 versus yoked saline (sal); ^## p < 0.01 versus yoked cocaine. In control (yoked saline) rats, the absolute SOD activity was 3.2 ± 0.14 U/mg protein in the liver, 5.8 ± 0.19 U/mg protein in kidney and 5.4 ± 0.74 U/mg protein in the heart. N = 6–8 rats/group

Fig. 9

MDA concentration in peripheral organs after cocaine (coc) self-administration and extinction training by yoked-triad procedure. Data are shown as mean ± SEM; **p < 0.01 versus yoked saline (sal); ^### p < 0.001 versus yoked cocaine. In control (yoked saline) group, the absolute MDA level was 27.44 ± 2 μM/g tissue in the liver, 332 ± 10.17 μM/g tissue in kidney and 19.15 ± 1.0 μM/g tissue in the heart. N = 6–8 rats/group