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.
Frankel
P S
PS
Department of Anatomy SL49, Tulane University School of Medicine/Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.pfranke@mailhost.tcs.tulane.edu
Harlan
R E
RE
Garcia
M M
MM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002421:Caudate Nucleus / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D011699:Putamen / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology*
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012702:Serotonin Antagonists; D014326:Tropanes; D009020:Morphine; C042253:bemesetron