Comparison of the effect of buspirone and 1-(2-pyrimidinyl)-piperazine on cerebral glucose utilization in the rat.
The novel anxiolytic and antidepressant, buspirone, and its main metabolite 1-(2-pyrimidinyl)-piperazine (1-PP), which is pharmacologically active, were examined for their effect on regional cerebral glucose utilization in awake rats using quantitative 2-deoxyglucose autoradiography. At a dose of 1 mg/kg, buspirone reduced glucose utilization in the hippocampus by approximately 15%, whilst 1-PP at the same dose had no effect. In comparison, at a higher dose, 10 mg/kg of both buspirone and 1-PP decreased glucose utilization in the hippocampus by 20% and 27%, respectively. In addition, widespread reductions in local cerebral glucose utilization were noted with this higher dose of 1-PP; such generalized effects are compatible with those reported for alpha 2 adrenoceptor antagonists. Buspirone at 1 and 10 mg/kg increased glucose utilization by 40% and 65%, respectively, in the lateral habenular nucleus, whilst 1-PP at 1 and 10 mg/kg had no effect. The findings suggest that buspirone's effects on glucose utilization cannot be attributed to 1-PP, unless high doses of buspirone are administered.
Grasby
P
P
M.R.C. Unit, Radcliffe Infirmary, Oxford, UK.
Sharp
T
T
Moorman
J
J
Grahame-Smith
D
D
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002065:Buspirone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D014151:Anti-Anxiety Agents; D003847:Deoxyglucose; C037921:1-(2-pyrimidinyl)piperazine; D005947:Glucose; D002065:Buspirone