Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study

Abstract

Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly increased the release of glutamate, which may cause neurotoxicity. Simultaneously, cocaine challenge after withdrawal also significantly increased the release of taurine, which counteracts glutamate-mediated excitotoxicity and possibly cell death. Thus, the mammalian brain has an endogenous self-protective mechanism against cocaine-mediated neurotoxicity and potentially addiction.

Fig. 1. Extracellular release of glutamate and taurine in striatum after acute cocaine treatment

30-minutes before the microdialysis assay rats were injected intraperitoneally with 10mg/kg cocaine or an equal volume of saline (controls). There were no significant changes in synaptic levels of glutamate (A) or taurine (B) by the Two-tailed t-test: (A) t=0.004904 df=7; P>0.05; (B) t=0.9954 df=7; P>0.05. Error bars, s.e.m.; n=8 in A and B.

Fig. 2. Extracellular release of glutamate and taurine in striatum after chronic cocaine treatment

Two groups of rats were injected intraperitoneally with 10mg/kg cocaine or equal volume of saline (controls) six-days per week for three-weeks. Microdialysis was initiated 24-hours after last injection of cocaine. (A) Basal level of glutamate in the cocaine group was significantly decreased compared to controls (Two-tailed t-test: t=5.588 df=6; **P<0.05). (B) Basal taurine levels were increased by 37% compared to controls, however, this change was not statistically significant (Two-tailed t-test: t=1.370 df=6; P>0.05). Error bars, s.e.m.; n=7 in A and B.

Fig. 3. Extracellular release of glutamate and taurine in striatum of chronic cocaine-treated rats measured after a cocaine “challenge”

Rats received 10 mg/kg cocaine (i.p.) for six days per week for three weeks. 24 hours after the last chronic cocaine dose, rats were challenged with 10 mg/kg cocaine (i.p.) or an equal volume of saline (i.p.) 30 minutes before microdialysis. There was a significant increase in both extracellular glutamate (A) (Two-tailed t-test: t=2.456 df=6; *P<0.05) and taurine (B) (Two-tailed t-test: t=4.469 df=6; **P<0.05). Error bars, s.e.m.; n=7 in A and B.