| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1995: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Research Abstract |
The interactins of methamphetamine (MAP), cocaine (COC) and alcohol on open-field behavior and extracellular striatum dopamine (DA) and serotonin (5HT) responses in rats were examined. Rats were observed for their behavior including the number of locomotions and rearing, and expression of stereotypy under the influence of MAP (4mg/kg, IP), COC (40mg/kg, IP), ALC (2g/kg, IP), and MAP+ALC and COC+ALC during 60 minutes. Extracellular dopamine (DA) and serotonin (5HT) levels in the striatum of freely moving rats were also measured using in vivo micro-dialysis during each challenge of the drug. The MAP produced marked increase in locomotion and rearing and raised the manner of stereotypy. The COC also showed less enhancement of locomotion, rearing and stereotypy than those induced by MAP.The ALC had no notici-able change in behaviors oberved in the open field. Co-administration of MAP with ALC showed more prolonged and enhanced excitation including locomotion than the single administration
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of MAP,and a decrease in frequency of rearing and degree of stereotypy, whereas co-administration of COC with ALC induced severe inactivation on open field behavior. An elevation in DA and 5HT levels that plateaued approximately from 40 to 60 minutes after MAP and MAP plus ALC treatment was more tolerant compared to other drug treatment. DA levels by MAP treatment after 60 minutes were increased to 1400% of pre-levels of drug treatment, and were increased to 1000% by MAP+ALC,the difference of alteration being statistically significant. Variations of DA and 5HT induced by other drug treatments were not significant. 5HT levels were increased to 2000% of pre-levels of drug-pretreated striatum by MAP and 2400% by MAP plus ALC,the difference of alteration being statistically not significant, whereas those in the striatum treated by other drugs showed no significant alteration.
Thus, MAP-induced psychostimulant behaviors concurrently and significantly increased, but appeared to be more relative with the co-administration of ALC.Since administration of MAP caused enhancement of both extracellular DA and 5HT contents in rat's striatum, in particular for the DA content by co-administration with ALC,indicating that excitatory effects of MAP in strongly associated with both DA and 5HT.Extracellular neurotransimission is the striatum supports the supplementary function of 5HT-ergic mechanism with DA-ergic activity. The findings confirm that co-administration of ALC with MAP is a potent drug treatment to produce neurotoxic effects following the regulation of DA,in particular, 5HT release. Less
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