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...

Multiple Memories in Multiple Systems

To describe how drug-associated learning might produce compulsive behaviors, it is necessary to have some overall conception of how different forms of learning occur and how they are normally orchestrated in the service of adaptive behavior. It is now well established that there are multiple memory systems in the mammalian brain (reviewed in 12,13). These memory systems are functionally semi-independent, and often concerned with distinct aspects of the animal's experience. Although the learning...

Introduction

Degeneration of dopaminergic neurons in the substantia nigra is a hallmark of Parkinson's disease (PD). However, despite decades of research, the cause of PD and the underlying mechanism of action responsible for the progressive degeneration of nigral dopaminergic neurons remain poorly understood (1). The creation of rodent and primate models for PD has provided a valuable tool in the study of the pathogenetic progression of the disease (2). On the other hand, primary neural cell cultures have...

Fields of Application of ED

DA, NA, and 5-HT represent three major neurotransmitters in the mammalian central nervous system (CNS). Their wide distribution in brain, their involvement in CNS pathologies such as psychosis and depression, the relevant role they play in the effects of drugs of abuse, and in behavior in general, has promoted an endless series of research that has provided an enormous contribution to knowledge of CNS function. This extraordinary success is mainly the result of the relative ease of measuring...

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...