| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
The purpose of the present research was to investigate central mechanism of psychic dependence and psychotoxicity produced by abused drugs. The drugs tested were methamphetamine (MAP) as a drug with psychotoxicity, and nicotine (NCT) as a drug without psychotoxicity. In a conditioned place preference (CPP) paradigm, both of MAP and NCT induced CPP after subcutaneous and intra-accumbens administration, however, NCT but not MAP induced CPP after administration into the medial prefrontal cortex. In a drug discrimination paradigm, MAP did not substitute for NCT in rats discriminating NCT from saline, and NCT did not substitute for MAP in rats discriminating MAP from saline, using the trainig dose of MAP and NCT which was equivalent to that inducing CPP.Both of subcutaneous MAP and NCT produced a progressive enhancement (sensitization) in the increasing effects on motor activity following repeated administration. A microdialysis study showed that MAP increased the dopamine (DA) levels in the nucleus accumbens, and NCT tended, but not significantly, to increase the DA levels in drug-naive rats, and that MAP showed a decrease and NCT showed an increase in their acute effects in rats sensitized to each drug. These results indicate that the reinforcing effects of MAP and NCT are mediated throught the reward system, however, the sites and mode of action of these drugs are different. The present study also suggest that the differential effects of MAP and NCT on the reward system may be implicated in the difference in the pharmacological characteristics of these drugs.
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