References

Bjorklund, A. and Lindvall, O. (1984) Dopamine-containing systems in the CNS, in Handbook of Chemical Neuroanatomy, Vol. 2 Classical Transmitters in the CNS, Part I (Bjorklund, A. and Hokfelt, T., eds.), Elsevier, Amsterdam, pp. 55-122. 2. Le Moine, C., Normand, E., and Bloch, B. (1991) Phenotypical characterization of the rat striatal neurons expressing the D1 dopamine receptor gene. Proc. Natl. Acad. Sci. USA 88, 4205-4209. 3. Gerfen, C. R., Enber, T. M., Susel, Z., et al. (1990) D1 and D2...

Introduction

Chronic drug abuse is a complex behavioral and social phenomenon, that stems from a diverse set of underlying neural mechanisms. However, two defining features of drug addiction make it especially difficult to treat. First, addiction is compulsive individuals often continue or resume drug use despite a conscious, stated wish to quit. Second, it is persistent relapse to active drug use can occur despite years of abstinence. This chapter discusses evidence that the inappropriate engagement of...

The Acute and Subacute Mouse MPTP Model

To induce a robust depletion of striatal DA in mice, large doses of MPTP and frequent injections are required. In mouse studies, MPTP is commonly administered either by an acute or subacute regimen. The acute MPTP studies generally follow the model that was initially examined by Sonsalla and Heikkila (38), who injected mice four times with 20 mg kg of MPTP at 1- or 2-hr intervals within a day. With this acute model, it was indicated that most mice do not survive after three or more injections...

The Chronic Mouse MPTPProbenecid Model

Pharmacokinetic consideration could be one of the underlying reasons why acute and subacute MPTP injections do not produce a sustained neurological insult in laboratory animals. It has been established that MPTP in rodents, following its peripheral administration, is rapidly excreted through the kidney (62). After reaching the central nervous system (CNS), this toxin and its active metabolite, MPP+, are quickly cleared from the brain (63). Hence, investigators tend to intensify MPTP...