GLUCOSE INJECTIONS INTO THE MEDIAL SEPTUM REVERSE THE EFFECTS OF INTRASEPTAL MORPHINE INFUSIONS ON HIPPOCAMPAL ACETYLCHOLINE OUTPUT AND MEMORY

Morphine infusions into the medial septum produce memory deficits whic h can be attenuated by concurrent intraseptal injections of glucose. T he mnemonic deficits following intraseptal morphine injections may be due, in part, to opioid inhibition of cholinergic neurons projecting t o the hippocampus, with glucose reducing this effect. The present expe riment determined whether glucose injections into the medial septum at tenuate the effects of intraseptal morphine injections on hippocampal acetylcholine release and on memory. Samples of extracellular acetylch oline levels were assessed at 12-min intervals using in vivo microdial ysis with high-performance liquid chromatography with electrochemical detection. Intraseptal morphine injections (4.0 nmol) reduced acetylch oline output starting at 12 min and lasting up to 72 min post-injectio n. Glucose (18.3 nmol) injected concomitantly with morphine reversed t he morphine-induced decrease in acetylcholine output. Several days aft er microdialysis testing, rats received drug infusions in the septum 2 0 min prior to spontaneous alternation testing. Intraseptal morphine i nfusions reduced alternation scores; this behavioral effect was revers ed by concurrent glucose infusions. The effects of drugs infused into the septal area on spontaneous alternation performance and acetylcholi ne output were positively correlated. These findings suggest that memo ry deficits induced by intraseptal morphine injections may result, at least partially, from a decrease in the activity of cholinergic neuron s and that this effect is reversed by glucose.