Elsevier

Neuroscience

Volume 87, Issue 3, 4 August 1998, Pages 551-558
Neuroscience

The neurosteroid pregnenolone sulfate infused into the nucleus basalis increases both acetylcholine release in the frontal cortex or amygdala and spatial memory

https://doi.org/10.1016/S0306-4522(98)00174-2Get rights and content

Abstract

The effects of an infusion (5 ng) of the neurosteroid pregnenolone sulfate into the nucleus basalis magnocellularis on acetylcholine release in the frontoparietal cortex and basolateral amygdala were evaluated during the 130 min post-injection in male Sprague–Dawley rats using in vivo microdialysis coupled “on line” with high performance liquid chromatography detection. One week later, the same animals were tested for spatial memory after another infusion of pregnenolone sulfate (5 ng) into the nucleus basalis. Results show that pregnenolone sulfate enhanced acetylcholine release by more than 50% of baseline concentrations in the two structures relative to a control injection. The duration of this effect was longer in cortex (130 min) than in amygdala (30 min). Furthermore, pregnenolone sulfate improved memory performance in a task based upon spatial recognition of a familiar environment. A significant positive correlation (r=0.49) was found between the recognition score in the spatial memory test and the levels of acetylcholine release in the frontoparietal cortex but not in the basolateral amygdala.

Therefore, our results suggest that the nucleus basalis magnocellularis-cortical pathway could be in part responsible for the promnesic effect of pregnenolone sulfate. This neurosteroid acts as a negative modulator of the GABAA receptor complex and positively modulates the N-methyl-d-aspartate receptor, possibly resulting in a global stimulatory effect on central cholinergic neurotransmission.

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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