Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [11C]methamphetamine in methamphetamine sensitized dog: Application of PET to drug pharmacokinetic study

doi:10.1016/S0969-8051(96)00204-1

Nuclear Medicine and Biology

Volume 24, Issue 2, February 1997, Pages 165-169

https://doi.org/10.1016/S0969-8051(96)00204-1 Get rights and content

Abstract

Repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the maximum accumulation level of [¹¹C]MAP in the MAP-sensitized dog brain was 1.4 times higher than that in the control. In behavioral studies, haloperidol (a dopamine D₂ receptor antagonist) prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake blocker) has the cross-behavioral sensitization with MAP. In the present study, to elucidate the relation between the MAP-induced behavioral sensitization and the pharmacokinetics of MAP, we investigated the effects of haloperidol and cocaine pretreatments on brain regional distribution and kinetics of [¹¹C]MAP using positron emission tomography (PET). A significant increase of [¹¹C]MAP uptake into the sensitized dog brain was prevented by haloperidol and cocaine pretreatments. These pharmacokinetic changes were not due to the changes in the rate of MAP metabolism. These results suggest haloperidol and cocaine can change the cerebral pharmacokinetic profile of MAP in the behavioral-sensitized dog. The variations of MAP-accumuation may affect the development or expression of MAP-induced behavioral sensitization.

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There have been some PET studies of the behavioural sensitization of animals to psychostimulant drugs (a putative model of schizophrenia). For example, repeated doses of methamphetamine evoked sensitization in dogs and increased the cerebral trapping of [11C]-methamphetamine (Nakamura et al., 1997). However, this finding is difficult to interpret, since the mechanism of methamphetamine binding in brain is unknown.
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^☆: Part of this research was supported by a scientific research fund from the Ministry of Welfare of the Japanese government.

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Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [11C]methamphetamine in methamphetamine sensitized dog: Application of PET to drug pharmacokinetic study☆

Abstract

Appl. Radiat. Isot.

J. Pharm. Sci.

Nucl. Med. Biol.

Nucl. Med. Biol.

Nucl. Med. Biol.

Brain Res.

Solid-phase extraction and GCMS quantitation of cocaine, ecgonine methyl ester, benzoylecgonine, and cocaethylene from meconium, whole blood, and plasma

J. Anal. Toxicol.

Kinetics of cocaine distribution, elimination, and chronotropic effects

Clin. Pharmacol. Ther.

Measurement of D2 dopamine receptor specific carbon-11-YM-09151-2 binding in the canine brain by PET: Importance of partial volume correction

J. Nucl. Med.

Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [¹¹C]methamphetamine in methamphetamine sensitized dog: Application of PET to drug pharmacokinetic study☆

Solid-phase extraction and $GC MS$ quantitation of cocaine, ecgonine methyl ester, benzoylecgonine, and cocaethylene from meconium, whole blood, and plasma