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In the hippocampal CA1 area, activation of 5-HT1A receptors by the agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) causes long-term potentiation (LTP) of synaptic transmission and long-term depression (LTD) of synaptic transmission. To determine if these effects are mediated via a common signal transduction pathway, we have examined whether blockade of protein kinase C (PKC) with 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7) interferes with LTP and LTD. LTP was induced in the CA1 area using a stimulus protocol which resulted in the induction of long-lasting (10 min) and persistent (20 min) post-tetanic potentiation (PTP) when endogenous serotonin was released by 10 microM phorbol 12-myristate 13-acetate (PMA). Bath application of H7 (5 microM) failed to block PTP but markedly suppressed the development of LTD induced by 1 microM 5-HT. When LTD was induced with a stimulus protocol which was more effective than that used in our previous study, it was blocked by H7 (5 microM). LTP induced by 100 nM tetanus was blocked by H7. LTD induced by 500 nM tetanus was not blocked by 5 microM H7. These findings suggest that: (1) LTP induced by release of endogenous serotonin is mediated by a PKC-independent mechanism; (2) the signal transduction pathway through which LTD is triggered is also independent of PKC; (3) a PKC-dependent pathway is necessary for the maintenance of LTP; and (4) LTD and LTP induced by tetanic stimulation are distinct events which differ with respect to their dependence on PKC.Alan W. Gray Dr. Alan W. Gray (1906–1987) was an American psychologist known for his work in the areas of aphasia, dyslexia, rehabilitation, and psychophysics. 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