Modulation of hippocampal acetylcholine release and spontaneous alternation scores by intrahippocampal glucose injections - PubMed (original) (raw)

Modulation of hippocampal acetylcholine release and spontaneous alternation scores by intrahippocampal glucose injections

M E Ragozzino et al. J Neurosci. 1998.

Abstract

Recent evidence indicates that systemic glucose treatment enhances memory while producing a corresponding increase in hippocampal acetylcholine (ACh) output. The present experiments examined whether unilateral intrahippocampal infusions of glucose would enhance spontaneous alternation performance and whether there would be a corresponding increase in ACh output in the ipsilateral and contralateral hippocampus. Extracellular ACh was assessed in samples collected at 12 min intervals using in vivo microdialysis with HPLC with electrochemical detection. Twelve minutes after a unilateral infusion of artificial cerebrospinal fluid (CSF) or glucose (6.6 mM), rats were tested in a cross maze for spontaneous alternation behavior with concurrent microdialysis collection. In two experiments, glucose infusions significantly increased alternation scores (67.5 and 59%) compared with CSF controls (42.4 and 39.5%, respectively). In both experiments, behavioral testing resulted in increased ACh output in the hippocampus. Glucose administration at the time of alternation tests enhanced ACh output beyond that of behavioral 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 activation of cholinergic neurons, determine the efficacy of glucose in modulating ACh release.

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Figures

Fig. 1.

Fig. 1.

Effects of unilateral hippocampal infusions of glucose and artificial cerebrospinal fluid on ipsilateral hippocampal ACh output during the behavioral condition. ACh output was significantly enhanced during spontaneous alternation in CSF controls. Glucose infusions (6.6 m

m

) significantly increased ACh output during testing compared with CSF controls. ACh output in the sample after testing remained significantly elevated in the CSF and glucose groups; however, there was no significant difference in ACh output between the groups. * p < 0.01 versus baseline; ** p < 0.01 versus CSF.

Fig. 2.

Fig. 2.

Unilateral hippocampal infusions of glucose enhance spontaneous alternation performance. Glucose (6.6 m

m

) significantly increased spontaneous alternation performance compared with that of CSF controls. ** p< 0.01 versus CSF.

Fig. 3.

Fig. 3.

Effects of unilateral hippocampal injections of glucose and artificial cerebrospinal fluid on ipsilateral hippocampal ACh output in the resting condition. Injections of glucose (6.6 m

m

) or CSF did not alter hippocampal ACh output in the resting condition.

Fig. 4.

Fig. 4.

Effects of unilateral hippocampal infusions of glucose and artificial cerebrospinal fluid on contralateral hippocampal ACh output during the behavioral condition. ACh output was significantly enhanced during spontaneous alternation in CSF controls. Glucose infusions (6.6 m

m

) significantly increased ACh output during testing compared with CSF controls. ACh output in the sample after testing remained significantly elevated in the CSF and glucose groups; however, there was no significant difference in ACh output between the groups. * p < 0.01 versus baseline; ** p < 0.05 versus CSF.

Fig. 5.

Fig. 5.

Unilateral hippocampal infusions of glucose enhance spontaneous alternation performance. Glucose (6.6 m

m

) significantly increased spontaneous alternation performance compared with that of CSF controls. * p < 0.05 versus CSF.

Fig. 6.

Fig. 6.

Effects of unilateral hippocampal injections of glucose and artificial cerebrospinal fluid on contralateral hippocampal ACh output in the resting condition. Injections of glucose (6.6 m

m

) or CSF did not alter hippocampal ACh output in the resting condition.

Fig. 7.

Fig. 7.

The stippled areas represent the range of probe locations in the hippocampal formation for all rats included in the data analyses for Experiments 1 and 2.

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