Methylxanthine effects on caudate dopamine release as measured by in vivo electrochemistry.

The effects of caffeine (1,3,7-trimethylxanthine) and theophylline (1,3-dimethylxanthine) on caudate dopamine release were examined in urethane anesthetized and freely moving rats using in vivo electrochemistry. In anesthetized animals, all doses (150, 250, and 500 mumole/kg, i.p.) produced significant decreases in caudate dopamine (DA) release, which were 14%, 30% and 58%, respectively, at 30 min. The decrease in caudate DA release appeared to be a selective effect with respect to drug and brain region. D-amphetamine (37 mumole/kg, i.p.) increased the caudate signal over a 150 min period. Caffeine, 250 mumole/kg, increased norepinephrine (NE) release in hippocampus by 37% at 30 min and 58% at 150 min. Motor cortical NE release was increased by 8% at 30 min and 44% at 150 min. In freely moving rats, caffeine and theophylline, 75 mumole/kg, increased caudate DA release by 39% and 66%, respectively, at 60 min. Caffeine, 250 and 500 mumole/kg, decreased caudate DA release by 31% and 52%, respectively, at 30 min. Theophylline, 250 mumole/kg, increased release by 25% at 75 min. A 500 mumole/kg dose of theophylline decreased caudate DA release by 44% at 30 min. Measurement of caudate methylxanthine concentrations showed that caudate caffeine levels were significantly higher than those of theophylline. These data are the first to show in an intact animal that methylxanthines affect the regional release of catecholamines (CA) in the central nervous system. This effect is dose dependent.