Extracellular catecholamine levels in rat hippocampus after a selective alpha-2 adrenoceptor antagonist or a selective dopamine uptake inhibitor: evidence for dopamine release from local dopaminergic nerve terminals.
The effect of 6-chloro-2,3,4,5-tetrahydro-3-methyl-1-H-3-benzazepine (SKF 86466), a selective nonimidazoline alpha-2 adrenoceptor antagonist, on hippocampal release of norepinephrine and dopamine in conscious rats was investigated by in vivo microdialysis and high-pressure liquid chromatography. Additionally, extracellular concentrations of hippocampal dopamine (DA) and norepinephrine (NE), during infusion of selective monoamine uptake inhibitors, were determined in freely moving rats. The basal concentration of NE in the dialysate was 4.9 +/- 0.3 pg/20 microliters. Intravenous administration of 5 or 10 mg/kg of SKF 86466 was associated with a transient increase (30 min) of 2-fold (12 +/- 1 pg/20 microliters; P < .05) and 8-fold (39 +/- 3 pg/20 microliters; P < .05), respectively, in dialysate NE, whereas a 1-mg/kg dose had no effect. DA was not detected in basal dialysates, but after the administration of 5 or 10 mg/kg of SKF 86466, 3.9 +/- 0.4 and 6.4 +/- 0.6 pg/20 microliters, respectively, was present in the dialysates. The maximum increase in dialysate DA was reached 60 to 90 min after SKF 86466. The DA was not derived from plasma because plasma NE was elevated after the 5 mg/kg dose of SKF 86466 whereas no plasma DA was detected. In order to determine whether DA was present in noradrenergic nerve terminals, the dopamine beta-hydroxylase inhibitor SKF 102698 was administered (50 mg/kg i.p.). The inhibitor decreased dialysate NE but DA was still not detected in the dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)
Xu
K
K
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Näveri
L
L
Frerichs
K U
KU
Hallenbeck
J M
JM
Feuerstein
G
G
Davis
J N
JN
Sirén
A L
AL
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors; D006624:Hippocampus / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
C052414:1-(3,5-difluorobenzyl)imidazole-2-thiol; D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D007093:Imidazoles; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; C043425:vanoxerine; D004299:Dopamine beta-Hydroxylase; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine; C039139:benalfocin