Effects of chronic amphetamine treatment on the glutamate concentration in cerebrospinal fluid and brain: implications for a theory of schizophrenia.

In rats, chronic (12 days) amphetamine administration (5 mg/kg, s.c.) resulted in more than 30% decrease of the glutamate content in the cerebrospinal fluid (CSF) and concomitant increase of glutamate levels in the frontal cortex, striatum and hippocampus. In contrast, chronic amphetamine had no effect on the GABA contents in these areas. The data are compatible with the interpretation that amphetamine induces an increase of dopaminergic function in these brain regions which results in an enhanced inhibition of glutamate release. It is hypothesized that diminished glutamate release accompanies the amphetamine psychosis as well as schizophrenia.