The effects of cocaine and the cocaine analog methyl-3-beta-(p-fluorophenyl)-1 alpha H, 5 alpha H-tropane-2b-carboxylate (CFT) on glutamate turnover rate were studied in the nucleus accumbens, striatum, frontal cortex, and parietal-cingulate cortex of the rat, using neurotransmitter turnover rate as an estimate of the activity of the glutamatergic neurons. Both cocaine [15 or 30 mg/kg, intraperitoneally (IP)] and CFT (2.2 mg/kg, IP) increased glutamate turnover in the nucleus accumbens, although the time course of their actions differed. These effects on glutamate turnover appeared at times after maximal motor activation of the animals had occurred. On the other hand, neither cocaine nor CFT affected glutamate turnover in the frontal cortex, parietal-cingulate cortex, or striatum. Neither cocaine nor CFT affected the content of glutamate or glucose in any brain region studied. Thus, although cocaine and CFT affect glutamatergic neurons in the CNS, these actions are not generalized across the CNS, but are restricted to a specific brain region.