Brain serotonin metabolism with relation to the head twitches elicited by lithium in combination with reserpine in mice

Abstract

Lithium alone, which scarcely induced head twitches, did not affect brain 5-hydroxytryptamine (5-HT) levels but increased 5-hydroxyindoleacetic acid (5-HIAA) levels. However, the combined use of lithium chloride (2 mEq/kg x 5, SC) and reserpine (5 mg/kg, SC) administered hourly markedly elicited the head twitches, together with the pronounced decrease of 5-HT levels and increase of 5-HIAA levels as similarly seen by reserpine alone. Pretreatment with p-chlorophenylalanine (PCPA) strongly potentiated the twitches elicited by the combined administration of lithium and reserpine, along with inducing the significant decrease of 5-HT levels and no change of 5-HIAA levels as compared with those levels in the PCPA-treated mice. The results imply that lithium produces the head twitches in the presence of reserpine, and an increase of 5-HIAA or a decrease of 5-HT levels do not necessarily interfere with the incidence of the twitches, and that the receptor sensitivity to 5-HT is strongly involved in the incidence of the head twitches.