Microdialysates of amines and metabolites from core nucleus accumbens of freely moving rats are altered by dizocilpine

Brain Res. 2001 May 25;902(1):108-18. doi: 10.1016/s0006-8993(01)02382-4.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Benzylamines / toxicity
  • Chromatography, High Pressure Liquid
  • Desipramine / pharmacology
  • Dizocilpine Maleate / pharmacology*
  • Dopamine / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Male
  • Microdialysis
  • Motor Activity / drug effects
  • Neuroprotective Agents / pharmacology*
  • Neurotransmitter Agents / metabolism*
  • Norepinephrine / metabolism
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Oxidopamine / toxicity
  • Rats
  • Rats, Wistar
  • Reserpine / toxicity
  • Serotonin / metabolism

Substances

  • Benzylamines
  • Excitatory Amino Acid Antagonists
  • Neuroprotective Agents
  • Neurotransmitter Agents
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Dizocilpine Maleate
  • Reserpine
  • Oxidopamine
  • DSP 4
  • Desipramine
  • Dopamine
  • Norepinephrine