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 administration 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 hypothesis that the serotonin-3 receptor (5-HT3R) is involved in morphine-induced IEG 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 rats were administered either morphine (10 mg/kg) or vehicle. Morphine significantly induced c-Fos expression in the dorsomedial CPu, as we have reported previously. Whereas MDL 72222 alone did not induce c-Fos, it potentiated the morphine-induced c-Fos expression. Morphine also induced JunB expression in the same region of the dorsomedial CPu. At 1 mg/kg, MDL 72222 both induced JunB expression and potentiated the response induced by morphine. At 10 mg/kg, MDL 72222 had no effect on basal JunB levels, but augmented the response to morphine. These findings demonstrate that the 5-HT3R antagonist, MDL 72222, can positively modulate morphine-induced IEG expression in the rat CPu in a dose dependent manner, in contrast to the reported suppressive effect observed when this antagonist is administered prior to amphetamine.[1]References
- The 5-HT3 receptor antagonist, MDL 72222, dose-dependently potentiates morphine-induced immediate-early gene expression in the rat caudate putamen. Frankel, P.S., Harlan, R.E., Garcia, M.M. Brain Res. (1998) [Pubmed]
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