Coadministration of dextromethorphan during pregnancy and throughout lactation prevents morphine-induced hyperprolactinemia in female rats

Abstract

Objective: To investigate whether coadministration of dextromethorphan (DM) could suppress morphine-induced hyperprolactinemia in female rats during pregnancy and throughout lactation.

Design: Controlled prospective study.

Setting: University research laboratory.

Animal(s): One hundred adult female Sprague-Dawley rats.

Intervention(s): Rats were randomly divided into four groups and were subcutaneously injected with either saline, morphine, morphine + DM, or DM alone twice a day, progressively increasing by 1 mg/kg at 7-day intervals from an initial dose of 2 mg/kg for both morphine and DM. Drug administration was continued during pregnancy. After the offspring were born, the doses injected into the dams were increased by 1 mg/kg every 2 weeks.

Main outcome measure(s): Serum prolactin (PRL) concentration and dopamine turnover rate at the hypothalamus and pituitary.

Result(s): Chronic morphine administration induced higher PRL concentrations than the control animals at mating, and at early and late pregnancy. In rats receiving DM coadministration, we did not observe any increase by morphine. Our neurochemical results showed that this effect of DM may be partly through blocking the effect of morphine on inhibition of tuberoinfundibular dopaminergic (TIDA) neuronal activity.

Conclusion(s): The use of DM as an adjuvant in females receiving chronic morphine treatment may prevent morphine-induced hyperprolactinemia.