Trifluoperazine inhibits hippocampal long-term potentiation and the phosphorylation of a 40,000 dalton protein.

Brief high frequency stimulation induces long-term potentiation (LTP) and changes in the endogenous phosphorylation of a 40,000 dalton protein in the hippocampus in a calcium-dependent manner. In the present paper we report that 40 microM trifluoperazine (TFP), a phenothiazine that binds calmodulin and blocks its activity, inhibits LTP in the hippocampal slice. In addition, calmodulin stimulates and TFP inhibits the phosphorylation of the 40,000 dalton protein (as well as that of several other proteins) in a dose-dependent fashion.