Effects of acute systemic treatment with the 5 HT-uptake blocker alaproclate on tissue levels and release of substance P in rat periaqueductal grey.
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 mumol/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 all 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 mumol/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.
Rosén
A
A
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Franck
J
J
Brodin
E
E
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009020:Morphine / Q000494:pharmacology; D015288:Neurokinin A / Q000378:metabolism; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism*
D015116:5,7-Dihydroxytryptamine; D000409:Alanine; D002766:Cholecystokinin; D009020:Morphine; D015288:Neurokinin A; D017367:Selective Serotonin Reuptake Inhibitors; D013373:Substance P; C025293:alaproclate