Figure 1.
Cocaine self-administration reduces glutamate transporter expression and function. A) [3H] glutamate uptake was significantly decreased in accumbens tissue slices following cocaine self-administration. A two-way ANOVA revealed significant main effects of cocaine treatment (F(1,26)=11.36, p=0.002) and glutamate concentration (F(2,26)=14.73, p<0.001); *p<0.05). B) The Vmax of glutamate uptake was reduced in cocaine subjects with no change in Kd. A two-way ANOVA revealed a significant effect of cocaine treatment (F(1,49)=11.21, p=0.001) and concentration of glutamate (F(4,49)=13.61, p<0.001). * p<0.05). C–E) Cocaine self-administration followed by 3 weeks of extinction training significantly decreased GLT-1 and xCT protein expression, and chronic treatment with N-acetylcysteine or ceftriaxone restored levels of both proteins. One-way ANOVA’s confirmed an effect of group for both GLT-1 (F(3,47)=5.34, p=0.003) and xCT (F(3,45)=4.47, p=0.008). *p<0.05 compared to cocaine. S=Saline; C=Cocaine; C-C=Cocaine+Ceftriaxone; C-N=Cocaine+N-acetylcysteine; M=Marker Ladder. F) Membrane fraction levels of GLT-1 and xCT were not changed in the prefrontal cortex following cocaine self-administration. G) Seven days of ceftriaxone treatment (200 mg/kg IP) had no effect on accumbens GLT-1 levels in naïve rats. H) Seven days of N-acetylcysteine treatment (100 mg/kg IP) had no effect on accumbens GLT-1 levels in naïve rats.