Simultaneous monitoring of dopamine, its metabolites and trans-isomer of atypical neuroleptic drug carbidine concentrations in striatal dialysates of conscious rats.

Journal Article

1. Transcerebral microdialysis was used to monitor dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and trans-isomer of atypical neuroleptic drug carbidine concentrations in the dialysates from dorsal striatum of freely moving rats following i.p. administration of the drug at doses 0.5, 1,5 and 25 mg/kg. The changes in locomotor activity as well as catalepsy in rats following transcarbidine administration were also evaluated. 2. The microdialysis "point of no net flux" method was used to measure interstitial free concentration (IFC) of trans-carbidine in the dorsal striatum of freely moving rats following i.p. administration of the drug at dose 5 mg/kg. The maximal IFC of trans-carbidine was found to be approximately 1 mu M 20-40 min after injection. 3. The drug at doses up to 1 mg/kg produces elevation of dopamine release not affecting sufficiently its metabolite dialysate levels. IFC of the drug calculated for these doses will not exceed 0.24 pM. At the dose 5 mg/kg, i.p., elevation of both dopamine release and metabolism was observed and dopamine release increased slightly more than DOPAC dialysate levels. 4. Stimulatory action of trans-carbidine on locomotor activity of non-operated rats has been observed at doses 0.2 and 0.5 mg/kg, i.p.. 5. Only the dose 25 mg/kg of trans-carbidine (maximal calculated IFC 4.53 mu M) was found to be cataleptogenic. The drug at this dose failed to increase DA release but induced a marked increase of DOPAC and HVA output. 6. It is concluded that trans-carbidine in in vivo neurochemical and behavioural studies demonstrates the preferential antagonistic action on dopamine release-regulating autoreceptors.

Full Text

Duke Authors

Cited Authors

  • Gainetdinov, RR; Sotnikova, TD; Grekhova, TV; Rayevsky, KS

Published Date

  • February 1996

Published In

Volume / Issue

  • 20 / 2

Start / End Page

  • 291 - 305

PubMed ID

  • 8861194

International Standard Serial Number (ISSN)

  • 0278-5846

Language

  • eng

Conference Location

  • England