Effects of trifluoperazine on the cholinergic function of the hippocampus of the rat.

The changes induced in the level and turnover rate (TRACh) of acetylcholine (ACh) in the hippocampus and in the in vitro release of [3H]ACh by intracerebroventricular injection of trifluoperazine (TFP) were studied. Rats were killed by microwave irradiation at various times after treatment with drug or vehicle and the levels of ACh were measured by gas chromatography. After the administration of 100 micrograms trifluoperazine, the content of ACh of the whole hippocampus increased from 24.0 +/- 2.9 to 35.2 +/- 4.2 nmols/g wet weight over a 60 min period, while the turnover rate was markedly decreased (from 0.86 to 0.53 nmols/min/g wet tissue weight). The potassium-evoked release of [3H]ACh from slices of hippocampus under in vitro conditions was decreased in a concentration-dependent manner by preincubation with 50 and 100 microM of trifluoperazine for 60 min. The results support the assumption that trifluoperazine can alter neurotransmission, possibly by inhibiting the calcium-binding protein calmodulin, and/or by interfering with cell metabolism.