title: Morphine self-administration into the lateral septum depends on dopaminergic mechanisms: Evidence from pharmacology and Fos neuroimaging.
abstract: Mice self-administer morphine into the lateral septum (LS), but the neuronal connections underlying this behaviour remain unknown. The present study tested whether the acquisition of intra-LS morphine self-administration depends on dopaminergic mechanisms. Mice were allowed to self-inject morphine (5 or 20ng/50nl) or vehicle directly into the LS using a spatial discrimination Y-maze task. Fos imaging was used to evaluate neuronal activation in cerebral structures directly connected to the LS or belonging to the dopaminergic system. The involvement of dopaminergic and opioidergic mechanisms was assessed by pre-treating naive mice peripherally with the D1 antagonist SCH23390, the D2/D3 antagonist sulpiride or the opiate antagonist naloxone before daily self-administration sessions. Mice acquired self-administration behaviour for intra-LS morphine that was associated with increased Fos expression in the ventral tegmental area (VTA), dorsal and ventral striatum and prefrontal cortex. Pre-treating animals with naloxone, SCH23390 or sulpiride completely prevented them from acquiring intra-LS morphine self-administration. All three antagonists consistently blocked Fos expression in the prefrontal cortex, but not in the VTA and striatum. Taken together, our results show that morphine self-administration into the LS depends on dopaminergic (D1 and D2/D3) and opioidergic mechanisms. Furthermore, they suggest that opioid peptides released in the LS could participate in regulating the activity of mesotegmental dopaminergic neurons.
authors.affiliation: Centre de Neurosciences Intégratives et Cognitives, Universités Bordeaux 1 et 2, UMR CNRS 5228, Avenue des Facultés, 33405 Talence, France. lemerrer@igbmc.u-strasbg.fr
authors.forename: Julie
authors.initials: J
authors.lastname: Le Merrer
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gavello-Baudy
authors.forename: Daniel
authors.initials: D
authors.lastname: Galey
authors.forename: Pierre
authors.initials: P
authors.lastname: Cazala
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D002452:Cell Count; D002755:Choice Behavior / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage*; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D011930:Reaction Time / Q000187:drug effects; D012646:Self Administration / Q000379:methods; D012686:Septal Nuclei / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D016761:Oncogene Proteins v-fos; D009270:Naloxone; D009020:Morphine; D013469:Sulpiride; D004298:Dopamine