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Estrogen enhancement of learning requires intact basal forebrain cholinergic neurons.

Gibbs RB (2001) Estrogen enhancement of learning requires intact basal forebrain cholinergic neurons. Neuroscience 2001 Abstracts 312.12. Society for Neuroscience, San Diego, CA.

Summary: We have shown that long-term continuous estrogen replacement, or weekly administration of estrogen plus progesterone, enhances acquisition of a delayed matching-to-position (DMP) spatial memory task. The present study examined whether hormone replacement enhances acquisition of the task after destroying basal forebrain cholinergic neurons with the selective immunotoxin 192IgG-saporin (SAP). Ovariectomized Sprague-Dawley rats received either SAP (1.0 Μg in 1.0 ΜL saline) or vehicle injected directly into the medial septum. Two weeks later, animals received either continuous estrogen replacement (E; 3 mm silastic capsule containing 17-β-estradiol, implanted s.c.) or weekly administration of estradiol (10 Μg in oil s.c.) followed two days later with progesterone (500 Μg in oil s.c.). Controls received sham implantation surgery and vehicle injections. DMP training began after 1 month of treatment. SAP injections significantly impaired acquisition of the DMP task (median days to criterion = 21.0 for SAP-treated animals vs. 14.0 for Ovariectomized controls; p<0.05). Neither continuous E replacement nor weekly administration of E+P significantly enhanced acquisition in the SAP-treated animals. Histology and hippocampal ChAT activity confirmed the loss of cholinergic cells in the medial septum and diagonal band of Broca in SAP treated animals. These findings suggest that cholinergic neurons in the medial septum/diagonal band are necessary for hormone-mediated enhancement of DMP acquisition. Studies using lower doses of SAP are currently underway.

Related Products: 192-IgG-SAP (Cat. #IT-01)

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