Citation

Shen H, Harvey BK, Chiang YH, Pick CG, Wang Y. Brain Res. 2011; 1368: 248-253.

Affiliation

National Institute on Drug Abuse, NIH, Baltimore, MD, U.S.A.

Copyright

(Copyright © 2011, International Brain Research Organization, Publisher Elsevier Publishing)

DOI

10.1016/j.brainres.2010.10.014

PMID

20950593

PMCID

PMC3014394

Abstract

We previously demonstrated that high doses of methamphetamine (MA) exacerbate damage induced by severe brain trauma. The purpose of the present study was to examine if MA, at low dosage, affected abnormalities in locomotor activity and dopamine turnover in a mouse model of mild traumatic brain injury (mTBI). Adult male CD1 mice were treated with MA (5 mg/kg i.p.) or vehicle 30-min prior to mTBI, conducted by dropping a 30 g metal weight onto the temporal skull, anterior the right ear. At 15 min after mTBI, animals were put into locomotor activity chambers for up to 72 hours. During the first 3 hours, mTBI alone, compared with vehicle control, did not alter total distance travelled. Treatment with MA significantly increased locomotor activity in the control animals during the first three hours; mTBI reduced MA-induced hyperactivity. In contrast, at 2 and 3 days after injury, mTBI or MA alone reduced locomotor activity. Co-treatment with MA and mTBI furtherreduced this activity, suggesting a differential and temporal behavioral interaction between MA and mTBI during acute and subacute phases after injury. Dopamine and DOPAC levels in striatal tissue were analyzed using HPLC-ECD. At one hour after mTBI or injection, DA was not altered but DOPAC level and DOPAC/DA turnover ratios were significantly reduced. Co-treatment with MA furtherreduced the DOPAC/DA ratio. At 36 hours after injury, mTBI increased tissue DA levels, but reduced DOPAC levels and DOPAC/DA ratios. Co-treatment with MA further reduced DOPAC/DA ratios in striatum. In conclusion, our data suggest that low dosage of MAworsens the suppression of locomotor responses and striatal dopamine turnover after mTBI.

Language: en