The 5-HT3 receptor antagonist, MDL 72222, dose-dependently potentiates morphine-induced immediate-early gene expression in the rat caudate putamen

Previous studies from this laboratory have demonstrated that acute administ ration of morphine induces the immediate-early genes (IEGs) c-Fos and JunB in the rat caudate putamen (CPu). In the present study, we tested the hypot hesis that the serotonin-3 receptor (5-HT3R) is involved in morphine-induce d IEC expression, using the selective antagonist to the 5-HT3R, MDL 72222, Rats were divided into three pretreatment groups: MDL 72222, 1 mg/kg or 10 mg/kg; or vehicle (DMSO). Thirty minutes following the pretreatment, the ra ts were administered either morphine (10 mg/kg) or vehicle. Morphine signif icantly induced c-Fos expression in the dorsomedial CPu, as we have reporte d previously. Whereas MDL 72222 alone did not induce c-Fos, it potentiated the morphine-induced c-Fos expression. Morphine also induced JunB expressio n in the same region of the dorsomedial CPu, At 1 mg/kg, MDL 72222 both ind uced JunB expression and potentiated the response induced by morphine. At 1 0 mg/kg, MDL 72222 had no effect on basal JunB levels, but augmented the re sponse to morphine. These findings demonstrate that the 5-HT3R antagonist, MDL 72222, can positively modulate morphine-induced IEG expression in the r at CPu in a dose dependent manner, in contrast to the reported suppressive effect observed when this antagonist is administered prior to amphetamine. (C) 1998 Elsevier Science B.V. All rights reserved.