MODULATION OF HIPPOCAMPAL ACETYLCHOLINE-RELEASE AND SPONTANEOUS-ALTERNATION SCORES BY INTRAHIPPOCAMPAL GLUCOSE INJECTIONS

Recent evidence indicates that systemic glucose treatment enhances mem ory while producing a corresponding increase in hippocampal acetylchol ine (ACh) output. The present experiments examined whether unilateral intrahippocampal infusions of glucose would enhance spontaneous altern ation performance and whether there would be a corresponding increase in ACh output in the ipsilateral and contralateral hippocampus. Extrac ellular ACh was assessed in samples collected at 12 min intervals usin g in vivo microdialysis with HPLC with electrochemical detection. Twel ve minutes after a unilateral infusion of artificial cerebrospinal flu id (CSF) or glucose (6.6 mM), rats were tested in a cross maze for spo ntaneous alternation behavior with concurrent microdialysis collection , In two experiments, glucose infusions significantly increased altern ation scores (67.5 and 59%) compared with CSF controls (42.4 and 39.5% , respectively), In both experiments, behavioral testing resulted in i ncreased ACh output in the hippocampus. Glucose administration at the lime of alternation tests enhanced ACh output beyond that of behaviora l testing alone both ipsilateral (+93.8%) and contralateral (+85%) to the infusion site, as compared with ACh output (+36.1% and +55.5%) of CSF controls, Glucose infusions did not affect hippocampal ACh output in rats kept in a holding chamber. These results suggest that glucose may enhance alternation scores by modulating ACh release, The findings also indicate that unilateral glucose infusions increase hippocampal ACh output both ipsilateral and contralateral to the site of injection , Furthermore, glucose increased ACh output only during maze testing, suggesting that specific behavioral demands, perhaps requiring activat ion of cholinergic neurons, determine the efficacy of glucose in modul ating ACh release.