Self-administration of the GABAA agonist muscimol into the medial septum: dependence on dopaminergic mechanisms.
BACKGROUND
Reinforcement in the medial septal division (MSDB) might involve local GABAergic mechanisms.


OBJECTIVE
We used intracranial self-administration to determine whether the GABAA agonist muscimol or antagonist bicuculline might have rewarding effects when infused into the MSDB. We assessed the anatomical specificity of muscimol intra-MSDB self-administration by injecting this molecule into the nucleus accumbens (NAc). Finally, we evaluated the involvement of dopaminergic mechanisms in muscimol self-administration.


METHODS
BALB/c mice were implanted with a guide cannula targeting the MSDB or the NAc. They were trained to discriminate between the two arms of a Y-maze, one arm being reinforced by muscimol or bicuculline injections. Another group of MSDB implanted mice was pre-treated intraperitoneally before muscimol self-administration with a D1 (SCH23390) or D2/D3 (sulpiride) receptor antagonist or vehicle. A last group of MSDB mice received additional bilateral guide cannulae targeting the ventral tegmental area (VTA) or a more dorsal region to assess the effects of intra-VTA injection of SCH23390 on intra-MSDB muscimol self-administration.


RESULTS
Mice self-administered intra-MSDB muscimol (0.6, 1.2, or 12 ng/50 nl), but not bicuculline (1.5 or 3 ng/50 nl). Systemic pre-treatment with SCH23390 (25 microg/kg) or sulpiride (50 mg/kg) or bilateral injection of SCH23390 (0.25 microg/0.1 microl) into the VTA prevented acquisition of intra-MSDB muscimol self-administration.


CONCLUSIONS
The activation of GABAA receptors in the MSDB supports self-administration, and dopamine release from the VTA may be involved in the acquisition of this behaviour. The MSDB could represent a common brain substrate for the rewarding properties of drugs facilitating GABAA tone.
Gavello-Baudy
Stéphanie
S
Centre de Neurosciences Intégratives et Cognitives, Universités Bordeaux 1 et 2, UMR CNRS 5228, Avenue des Facultés, 33405, Talence, France. sgavello@aliceadsl.fr
Le Merrer
Julie
J
Decorte
Laurence
L
David
Vincent
V
Cazala
Pierre
P
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology; D001640:Bicuculline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003627:Data Interpretation, Statistical; D004298:Dopamine / Q000502:physiology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics; D008845:Microinjections / Q000379:methods; D009118:Muscimol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009714:Nucleus Accumbens / Q000187:drug effects; D010784:Photomicrography / Q000379:methods; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D012055:Reinforcement Schedule; D012646:Self Administration / Q000379:methods*; D012686:Septal Nuclei / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects; D014726:Vestibular Nuclei / Q000187:drug effects
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D058785:GABA-A Receptor Agonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D009118:Muscimol; C017069:bicuculline methiodide; D013469:Sulpiride; D004298:Dopamine; D001640:Bicuculline