BMY-14802 reverses the reduction of striatal dopamine release induced by (+)-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine.
Intraperitoneal injection of (+)-3-[3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3PPP), a sigma receptor agonist, significantly reduced the striatal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) measured by in vivo microdialysis. These reductions were significantly greater at (+)-3PPP doses of 12 and 24 mg/kg than at 1 mg/kg. The levels of 5-hydroxyindoleacetic acid (5HIAA) were increased by the injection of (+)-3PPP in dose of 24 mg/kg, but were not affected at lower doses. BMY-14802, a sigma antagonist, alone at doses of 15 mg/kg and 30 mg/kg did not affect the levels of DA, DOPAC, HVA and 5HIAA. Pretreatment with 30 mg/kg BMY-14802 reversed the reduction of the levels of DA induced by 12 mg/kg (+)-3PPP. Although neither 30 mg/kg BMY-14802 nor 12 mg/kg (+)-3PPP affected the levels of striatal 5HIAA, combined treatment with both produced a significant elevation. These findings clearly demonstrate that sigma receptors may regulate DA release from the striatal presynapse.
Department of Neuropsychiatry, Okayama University Medical School, Japan.
A
A
Kanzaki
K
K
Okumura
H
H
Ujike
K
K
Tsuchida
K
K
Akiyama
S
S
Otsuki
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000502:physiology; D013237:Stereoisomerism
D015259:Dopamine Agents; D010880:Piperidines; D011743:Pyrimidines; D017480:Receptors, sigma; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; C026539:preclamol; D004298:Dopamine