HIPPOCAMPAL ACETYLCHOLINE-RELEASE DURING MEMORY TESTING IN RATS - AUGMENTATION BY GLUCOSE

Several lines of evidence indicate that a modest increase in circulati ng glucose levels enhances memory. One mechanism underlying glucose ef fects on memory may be an increase in acetylcholine (ACh) release. The present experiment determined whether enhancement of spontaneous alte rnation performance by systemic glucose treatment is related to an inc rease in hippocampal ACh output. Samples of extracellular ACh were ass essed at 12-min intervals using in vivo microdialysis with HPLC-EC. Tw enty-four minutes after an intraperitoneal injection of saline or gluc ose (100, 250, or 1000 mg/kg), rats were tested in a four-arm cross ma ze for spontaneous alternation behavior combined with microdialysis co llection. Glucose at 250 mg/kg, but not 100 or 1000 mg/kg, produced an increase in spontaneous alternation scores (69.5%) and ACh output (12 1.5% versus baseline) compared to alternation scores (44.7%) and ACh o utput (58.9% versus baseline) of saline controls. The glucose-induced increase in alternation scores and ACh output was not secondary to cha nges in locomotor activity. Saline and glucose (100-1000 mg/kg) treatm ent had no effect on hippocampal ACh output when rats remained in the holding chamber. These findings suggest that glucose may enhance memor y by directly or indirectly increasing the release of ACh. The results also indicate that hippocampal ACh release is increased in rats perfo rming a spatial task Moreover, because glucose enhanced ACh output onl y during behavioral testing, circulating glucose may modulate ACh rele ase only under conditions in which cholinergic cells are activated.