Increasing acetylcholine levels in the hippocampus or entorhinal cortex reverses the impairing effects of septal GABA receptor activation on spontaneous alternation

Intra-septal infusions of the gamma -aminobutyric acid (GABA) agonist musci mol impair learning and memory in a variety of tasks. This experiment deter mined whether hippocampal or entorhinal infusions of the acetylcholinestera se inhibitor physostigmine would reverse such impairing effects on spontane ous alternation performance, a measure of spatial working memory. Male Spra gue-Dawley rats were given intra-septal infusions of vehicle or muscimol (1 nmole/0.5 muL) combined with unilateral intra-hippocampal or intra-entorhi nal infusions of vehicle or physostigmine (10 mug/muL for the hippocampus; 7.5 mug/muL or 1.875 mug/0.25 muL for the entorhinal cortex). Fifteen minut es later, spontaneous alternation performance was assessed. The results ind icated that intra-septal infusions of muscimol significantly decreased perc entage-of-alternation scores, whereas intra-hippocampal or intra-entorhinal infusions of physostigmine had no effect. More importantly, intra-hippocam pal or intra-entorhinal infusions of physostigmine, at doses that did not i nfluence performance when administered alone, completely reversed the impai ring effects of the muscimol infusions. These findings indicate that increa sing cholinergic levels in the hippocampus or entorhinal cortex is sufficie nt to reverse the impairing effects of septal GABA receptor activation and support the hypothesis that the impairing effects of septal GABAergic activ ity involve cholinergic processes in the hippocampus and the entorhinal cor tex.