Progressive augmentation of striatal and accumbal preprotachykinin mRNA levels by chronic treatment with methamphetamine and effect of concurrent administration of the N-methyl-D-aspartate receptor antagonist MK-801
Abstract
We have assessed the time course of repeated administration of methamphetamine (METH; 4 mg/kg) and withdrawal on the levels of preprotachykinin (PPT) and preproenkephalin (PPE) mRNA abundance in the caudate-putamen (CPu) and nucleus accumbens (NAc) of the rat brain by in situ hybridization histochemistry. Neostriatal PPT mRNA levels rose gradually between days 1 and 6 of treatment, with the greatest elevation observed at day 6. After 6 days of daily injections twice per day, PPT mRNA increases in dorsomedial (172%) and ventromedial (196%) aspects of the CPu were significantly higher than in dorsolateral (147%) and ventrolateral (135%) subdivisions. Similarly, PPT mRNA levels were increased in the anterior CPu (163%) and NAc (121%). Concurrent administration of METH and the NMDA receptor antagonist MK-801 attenuated METH-induced increases of PPT mRNA in all aspects of the CPu at day 6 of treatment and completely prevented the increase in the NAc. Moreover, animals treated with METH for 6 days and then withdrawn for 15 days displayed PPT mRNA levels in striatum and accumbens that were statistically indistinguishable from those of controls. Adjacent sections from the same brains were used to assess PPE mRNA levels. PPE mRNA levels...Continue Reading
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