Haloperidol causes irreversible damage to rat anterior pituitary lactotropes in culture

Haloperidol, in concentrations in excess of 10(-5)M promotes the release of prolactin from rat anterior pituitary cells in monolayer culture. Histologic evidence revealed that 10(-4)M concentrations cause an irreversible cytotoxic effect that resulted in a loss of cell membrane integrity and a massive release of intracellular prolactin into the surrounding medium. Paradoxically, at 10(-5)M, haloperidol significantly inhibited prolactin release and promoted an accumulation of intracellular secretory granules. Lower concentrations had no significant effect. Although it is nominally classified as a dopamine receptor blocker and can (in lower concentrations) inhibit dopamine's suppression of prolactin release, haloperidol in higher concentration enhances prolactin release by a cytotoxic mechanism unrelated to dopamine receptor interaction.