Self-administration of the GABAA agonist muscimol into the medial septum: dependence on dopaminergic mechanisms.

Rationale: Reinforcement in the medial septal division (MSDB) might involve local GABAergic mechanisms.

Objectives: 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.

Materials And 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.

Conclusion: 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.