Effects of acute systemic treatment with the 5 HT-uptake blocker alaproclate on tissue levels and release of substance P in rat periaqueductal grey

Abstract

The effects of acute systemic treatment with alaproclate, a serotonin uptake blocker on regional brain tissue levels of substance P, neurokinin A and cholecystokinin were studied in the rat. The peptide levels of all three peptides were increased (23–35%) in the rat periaqueductal grey 60 min after treatment with alaproclate (20 μmol/kg peroral, p.o.), compared to controls. In the cingulate cortex, the tissue levels of substance P and cholecystokinin were increased (19–32%) after subcutaneous (s.c.) treatment with alaproclate, compared to controls. Higher tissue levels of ail three peptides (20–38%) in the periaqueductal grey, and lower levels of substance P and cholecystokinin in the cingulate cortex were found following saline s.c. compared to saline p.o., probably due to different degrees of stress. In microdialysis experiments, a s.c. injection of either saline (2 ml/kg), alaproclate (20 μmol/kg) or morphine (3 mg/kg) was found to slowly increase the substance P release in the periaqueductal grey. Experiments with the selective 5-HT neurotoxin, 5,7-dihydroxytryptamine indicated no neuronal co-existence of substance P and serotonin in the periaqueductal grey and cingulate cortex. In conclusion, acute treatment with the serotonin uptake blocker alaproclate increases both the tissue level and the release of substance P in the periaqueductal grey.