Intraseptal infusions of muscimol impair spontaneous alternation performance: infusions of glucose into the hippocampus, but not the medial septum, reverse the deficit.

As observed with intraseptal injections of opioid receptor agonists, direct infusions of GABAergic receptor agonists into the medial septum impair performance on several tasks that involve spatial or working memory processes in rats. Because the effects of opioid-induced impairments can be reliably reversed by concomitant intraseptal infusions of glucose, the experiments reported here determined whether impairments produced by GABAergic agonists would similarly be reversed by glucose. The findings of Experiment 1 showed, in male Sprague-Dawley rats, that intraseptal infusions of the GABA agonist muscimol (1 or 3 nmol/0.5 microliter) impaired spontaneous alternation performance. The results of Experiment 2 indicated that intraseptal infusions of glucose (8, 17, or 33 nmol) or glutamate (15 or 30 nmol) did not attenuate the muscimol-induced deficit on spontaneous alternation performance, whereas infusions of the GABAergic antagonist bicuculline methiodide (0.1 nmol) did. However, the findings of Experiment 3 indicated that glucose injections (50 nmol/0.5 microliter) into the hippocampus did reverse the impairing effect of the intraseptal muscimol infusions. Combined, these findings suggest that the neurochemical regulation of learning and memory may involve hierarchical interactions between particular neurotransmitter and neuroanatomical systems. Specifically, medial septal GABAergic effects on spontaneous alternation prevail over those of glucose or glutamate in the medial septum, but are overridden by the effects of glucose in the hippocampus.