Caffeine induces dopamine and glutamate release in the shell of the nucleus accumbens

Abstract

An increase in the extracellular concentration of dopamine in the nucleus accumbens (NAc) is believed to be one of the main mechanisms involved in the rewarding and motor-activating properties of psychostimulants such as amphetamines and cocaine. Using in vivo microdialysis in freely moving rats, we demonstrate that systemic administration of behaviorally relevant doses of caffeine can preferentially increase extracellular levels of dopamine and glutamate in the shell of the NAc. These effects could be reproduced by the administration of a selective adenosine A1 receptor antagonist but not by a selective adenosine A2A receptor antagonist. This suggests that caffeine, because of its ability to block adenosine A1 receptors, shares neurochemical properties with other psychostimulants, which could contribute to the widespread consumption of caffeine-containing beverages.

Fig. 1.

Total horizontal motor activity after intraperitoneal administration of caffeine in habituated rats. The results represent means ± SEM of the accumulated motor activity counts during the first 60 min period of observation (n = 6 per group). Significant motor activation was obtained with caffeine in a dose of 10 mg/kg (CAFF 10) and caffeine in a dose of 30 mg/kg (CAFF 30). **p < 0.01 compared with the group treated with saline (SAL).CAFF 3 and CAFF 100indicate 3 and 100 mg/kg caffeine, respectively.

Fig. 2.

Extracellular concentrations of dopamine (DA) and glutamate (Glu) in the shell of the NAc after intraperitoneal administration of saline or caffeine [3 (caff 3), 10 (caff 10), 30 (caff 30), or 100 (caff 100) mg/kg]. The results represent means ± SEM of the percentage of basal values of the extracellular concentrations of dopamine and glutamate (n = 6–8 per group). Basal values were the means of three values before drug administration. Caffeine at doses of 10 and 30 mg/kg but not at doses of 3 and 100 mg/kg significantly increased the extracellular levels of dopamine and glutamate (Student's pairedt test; only significant results of pretreatment vs post-treatment are shown).

Fig. 3.

Extracellular concentrations of dopamine (DA) and glutamate (Glu) in the shell and core of the NAc after intraperitoneal administration of caffeine [30 mg/kg (caff 30)]. The results represent means ± SEM of the percentage of basal values of the extracellular concentrations of dopamine and glutamate (n = 6–8 per group). Basal values were the means of three values before drug administration. Caffeine (30 mg/kg) produced a significant increase in the extracellular concentration of dopamine, but not of glutamate, in the core of the NAc (Student's paired t test; only significant results of pretreatment vs post-treatment are shown). This effect was significantly different from that produced by 30 mg/kg caffeine in the shell of the NAc (interaction between area and treatment factors: p < 0.01 by repeated-measures ANOVA).

Fig. 4.

Extracellular concentrations of dopamine (DA) and glutamate (Glu) in the shell of the NAc after intraperitoneal administration of the adenosine A1 receptor antagonist CPT (4.8 mg/kg) and the A2A receptor antagonist SCH 58261 (2 mg/kg). The results represent means ± SEM of the percentage of basal values of the extracellular concentrations of dopamine and glutamate (n = 6–7 per group). Basal values were the means of three values before drug administration. CPT but not SCH 58261 produced a significant increase in the extracellular concentrations of dopamine and glutamate (Student's pairedt test; only significant results of pretreatment vs post-treatment are shown).