Microdialysates of amines and metabolites from core nucleus accumbens of freely moving rats are altered by dizocilpine.
In vivo microdialysis combined with high performance liquid chromatography (HPLC) with electrochemical detection, was used to study the effect of MK-801 (0.1 mg/kg i.p.) on extracellular concentrations of dopamine (DA) 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), norepinephrine (NE) and DOPAC/DA ratio in intact, 6-hydroxydopamine (6-OHDA)-lesioned, DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzyl-amine hydrochloride)-lesioned and reserpine-treated rats. The results revealed high basal DA (0.735+/-0.05 fmol/microl), DOPAC (195.93+/-20.18 fmol/microl) and NE (0.585+/-0.01 fmol/microl), low 5-HT (0.334+/-0.032 fmol/microl) and high DOPAC/DA ratio (265.11+/-20.73) in intact cACC. 6-OHDA alone (8 microg/2 microl) depleted DA (-66%), DOPAC (-65%), and NE (-62%). On the other hand, in desipramine (DMI)-pretreated rats, 6-OHDA induced a large depletion of DA (-94%), DOPAC (-97%) and reduced DOPAC/DA ratio (-73%), but increased NE to 142% of intact and 369% of 6-OHDA-lesioned rats. DSP4 (50 mg/kg) decreased NE (-97%), DOPAC (-75%) and DOPAC/DA ratio (-69%). Reserpine (5 mg/kg s.c.) significantly decreased DOPAC (-84%), DOPAC/DA ratio (-81%), 5-HT (-69%) and NE (-86%), but nonsignificantly increased DA. In the intact rats, MK-801 did not change DA, but increased DOPAC and DOPAC/DA ratio. In 6-OHDA-lesioned rats, MK-801 increased DA, whereas in 6-OHDA+DMI rats MK-801 additionally increased DOPAC and DOPAC/DA ratio. DSP4 and reserpine reduced the ability of MK-801 to increase DOPAC and DOPAC/DA ratio. MK-801 did not change NE concentration in dialysates collected from intact rats, but increased that from 6-OHDA+DMI-lesioned rats. In DSP4-lesioned and reserpine-treated rats, MK-801 increased NE but to a level lower than that observed in the intact rats. These results suggest that systemic administration of a low dose of MK-801, which induces profound locomotor stimulation without stereotypy, increases DOPAC and DOPAC/DA ratio in the cACC of intact rats, whereas it additionally increases the depleted DA and NE concentrations especially in 6-OHDA-lesioned rats pretreated with DMI.
Hatip-Al-Khatib
I
I
Department of Pharmacology, Faculty of Medicine, Pamukkale University, P.O. Box 33, 20027, Denizli, Turkey. izfunhatip2000@yahoo.com
Mishima
K
K
Iwasaki
K
K
Fujiwara
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001596:Benzylamines / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D003891:Desipramine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000633:toxicity; D012701:Serotonin / Q000378:metabolism
D001596:Benzylamines; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D016291:Dizocilpine Maleate; D012110:Reserpine; D016627:Oxidopamine; C012102:DSP 4; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine