The neurosteroid pregnenolone sulfate infused into the nucleus basalis increases both acetylcholine release in the frontal cortex or amygdala and spatial memory
Section snippets
Subjects
Male Sprague–Dawley rats (Iffa–Credo), weighing 260–280 g upon arrival, had ad libitum access to food and water and were housed individually. The light–dark cycle (lights were on from 8.00 a.m. to 8.00 p.m.), temperature (22°C), and humidity (60%) were kept constant in the animal house. Animals were allowed at least four days of acclimatization before experiments were started. All experiments were carried out in accordance with the European Communities Council Directive (96/609/EEC) on animal
Effects of pregnenolone sulfate administration into the nucleus basalis magnocellularis on extracellular concentration of acetylcholine in the frontoparietal cortex and basolateral amygdala
There were no differences in baseline extracellular concentrations of ACh between the treatment groups, either in cortex or in amygdala. The baseline mean efflux of ACh (mean±S.E.M.) expressed in fmol/min was 14.32±1.07 in the cortex and 26.86±2.77 in the amygdala. Saline intra-NBM injections were followed by a small increase in the outflow of ACh from the amygdala and from the cortex, lasting only one collection period, associated with the handling of the animal and probably due to stress.
As
Discussion
These experiments demonstrate that pregnenolone sulfate infusions into the NBM increase extracellular concentrations of ACh in the somatosensory frontoparietal cortex and in the basolateral amygdala. That is, the administration of pregnenolone sulfate directly in the cholinergic cell body region of the basal forebrain induces increased ACh release in the main projection structures. Increased ACh release has also recently been reported in another cholinergic terminal region, the hippocampus,
Conclusions
Pregnenolone sulfate administration (5 ng) at the level of cholinergic cell bodies in the NBM increases ACh release in the projection areas of those neurons, the basolateral amygdala and frontoparietal cortex. The ACh increase induced by pregnenolone sulfate administration is longer in the cortex (130 min) than in the amygdala (30 min). Post-acquisition pregnenolone sulfate administration (5 ng) into the NBM improves the spatial recognition of a familiar environment. Taken together, these results
Acknowledgements
The work of M. P. was supported by a post-doctoral fellowship from the Ministerio de Educacion y Cultura (Spain). J. D. was supported by the Human Frontiers Science Program.
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