CHRONIC DIAZEPAM TREATMENT IN RATS CAUSES LONG-LASTING CHANGES IN CENTRAL [H-3] 5-HYDROXYTRYPTAMINE AND [C-14] GAMMA-AMINOBUTYRIC ACID RELEASE

The effects of chronic diazepam administration to rats on the central release of [3H]-5-hydroxytryptamine ([3H]-5-HT) and [14C]-γ-aminobutyric acid ([14C]-GABA, ex vivo) were examined. Chronic (5 and 21 days) administration of diazepam (4 mg kg-1 i.p. daily for 21 days) reduced the K-evoked (20 mM KCl) release of [3H]-5-HT from frontal cortex by approximately 50%. Remarkably, this decrease was still present 1 week after diazepam withdrawal. Chronic diazepam treatment did not significantly affect hippocampal [3H]-5-HT release but after 21 days the K-evoked release of [14C]-GABA was more than doubled and remained elevated 30 h after withdrawal; it returned to control levels after 1 week, and decreased below control levels after 2 weeks. This study indicates that chronic diazepam treatment produces striking changes in transmitter release in rats that persist long after treatment has ceased.