Izzettin Hatip-Al-Khatib1,*, Funda Bölükbasi2, Kenichi Mishima3, Nobuaki Egashira3, Katsunori Iwasaki3 and Michihiro Fujiwara3
1Department of Pharmacology, Faculty of Medicine, Pamukkale University, Denizli, 20027 Turkey
2J&J Janssen-Cilag, Istanbul, 81610 Turkey
3Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan
*Corresponding author. FAX: +90-258-2132874, E-mail: firstname.lastname@example.org, email@example.com
Abstract: We investigated modification of the MK-801 effect on motor activity and extracellular amines concentration by 6-hydroxydopamine (6-OHDA)-induced lesion of core nucleus accumbens (cACC) of rats. In vivo microdialysis-HPLC showed that the concentrations (fmol/ml) of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and serotonin were 0.738 ± 0.135, 155.34 ± 41.01 and 0.334 ± 0.024, respectively, in the cACC of intact rats. The DOPAC/DA ratio was 264.24 ± 94.01. Unilateral lesion of the cACC with 6-OHDA (8 mg/ml) substantially reduced DA (−93%) and DOPAC (−97%) in desipramine (30 mg/kg, i.p.)-pretreated rats (6-OHDA+DMI rats) as compared to the 65% reduction rate of both amines in saline-pretreated rats (6-OHDA+saline rats). Moreover, DOPAC was reduced by 72% in 6-OHDA+DMI rats. MK-801 increased DOPAC (426-467%) and DOPAC/DA ratio (180-230%) in intact rats. On the other hand, MK-801 increased DA by 154% and 505% in 6-OHDA+saline and 6-OHDA+DMI rats, respectively. 6-OHDA reduced the effect of MK-801 on DOPAC and DOPAC/DA ratio. In the behavioral studies, MK-801 (0.01-0.3 mg/kg, i.p.) increased locomotor activity and rearing of intact rats. Bilateral 6-OHDA+DMI lesion of the cACC caused greater reduction in the effect of MK-801 (0.1 mg/kg) than that of the shell nucleus accumbens. These results suggest that increased extracellular DOPAC concentration (but not DA) and DOPAC/DA ratio in the cACC plays an important role in MK-801-hyperactivity.
Keywords: MK-801, Core nucleus accumbens (rat), Microdialysis, Motor activity
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