Regulation of Adult Neurogenesis and Gliogenesis by Abused Substances

Studies on dopaminergic roles in the regulation of adult cytogenesis are just emerging. Two recent reports have demonstrated that the midbrain dopa-minergic transmission that underlies major biological actions of psychostimulants can be a powerful regulator of adult cytogenesis. Teuchert-Noodt and co-workers found that acute treatment with methamphetamine at a high dose (25 or 50 mg kg) suppresses dentate granule cell proliferation by 28-34 in the adult gerbil hippocampus (36). Experiments...

Summary PFC and Other Cortical and Limbic Regions

Glutamate receptor expression in the PFC undergoes complex changes after drug administration is discontinued that depend on the withdrawal time and probably differ between cocaine and amphetamine, at least for NR1. In general, some results suggest that AMPA receptor subunit expression changes at early withdrawal times whereas NMDA receptor subunit expression is altered after longer withdrawals. Because relatively few studies have assessed glutamate transmission in the PFC of sensitized rats...

Summary VTA and Substantia Nigra

As reviewed in Subheading 2.1., both neurochemical and electrophysi-ological studies suggest that there is an enhancement in the responsiveness of VTA DA neurons to the excitatory effects of AMPA shortly after discontinuing repeated psychostimulant administration. An increase in AMPA receptor expression in the VTA would provide a simple explanation for these results. However, although Western blotting studies have found increased GluR1 and NR1 levels in the VTA shortly after cocaine...

Results in the NAc and Striatum

We have measured glutamate receptor subunit mRNA levels and immuno-reactivity in rats treated for 5 d with 5 mg kg of amphetamine or saline and perfused 3 or 14 d after the last injection. For AMPA receptor subunits, quantitative in situ hybridization studies showed no changes in GluR1-3 mRNA levels in the NAc after 3 d, but decreases in GluRl and GluR2 mRNA levels were observed after 14 d (41). Parallel changes were observed at the protein level using quantative immunoautoradiography (42)....

Beth Levant 1 Introduction

The central nervous system (CNS) dopamine system plays an important role in mediating the reinforcing effects of drugs of abuse (1). In addition, dopamine receptors have been the principal target of drugs employed in the treatment of neuropsychiatry disorders such as schizophrenia and Parkinson's disease. Until 1990, the dopamine receptor population in the brain and periphery was believed to consist of two subtypes, Dj and D2, which were distinguished by their pharmacology and coupling to...

Regulation of Adult Neurogenesis and Gliogenesis

A great deal of effort recently has been made in animal experiments to explore the regulation of adult neurogenesis gliogenesis in the CNS by a variety of experimental manipulations. Available data show that growth factors have significant effects on the behavior of neural progenitor's both in vivo and in vitro. For example, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) infused into the lateral ventricle of adult rats and mice profoundly increase proliferation of cells...

Research Models of PD

To establish a valid experimental model that closely resembles PD by keeping the cardinal symptomatology of human PD in mind (Table 1), the Major Clinical and Neuropathological Features of Human PD Major types of symptomatology Motor deficits Progressive nigral cell death Depletion of DA transmission Rigidity, bradykinesia, resting tremor, gait disturbance Gradual loss of TH-immunoreactive, dopaminergic neurons in the substantia nigra pars compacta Reduced level of striatal terminal DA, its...

Results in the VTA and Substantia Nigra

Using Western blotting, Nestler and colleagues found increased GluRl levels in the VTA of rats killed 16-18 h after discontinuation of repeated cocaine, morphine, ethanol, or stress paradigms (12,13). Increased GluR1 was not observed in the substantia nigra after repeated cocaine or morphine treatment (12). The substantia nigra was not examined in stress studies (12), but after repeated ethanol administration, there was a greater increase in GluR1 in the substantia nigra than in the VTA (13)....

Role of the VTA in Behavioral Sensitization

Many lines of evidence have suggested that the development of behavioral sensitization is associated with an increase in excitatory drive to VTA DA neurons (8). This provided the impetus for examining whether glutamate transmission is enhanced in the VTA during the early phase of drug withdrawal. The first evidence to support this hypothesis came from in vivo single-unit recording studies demonstrating that VTA DA neurons recorded from cocaine-or amphetamine-sensitized animals were more...

Role of Inflammation in Neurodegenerative Disorders

Previously, the brain has been considered an immune privileged environment partly owing to the existence of the brain-blood barrier. However, inflammatory responses in the brain have been increasingly associated with pathogenesis of several degenerative neurological disorders including Parkinson's disease (PD), Alzheimer's disease, AIDS dementia, and amyotrophic lateral sclerosis (ALS, 32-34). Two types of glial cells, namely microglia and astrocytes, are the primary players of the inflammatory...

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...

Materials

Male C57Bl 6 mice (n 6) (Charles Rivers, St Foie, PQ), 8-10 wk of age. 3. Dissecting microscope (Leica). 4. Artificial cerebrospinal fluid (aCSF) 26 mMNaHCO3, 124 mM NaCl, 5 mM KCl, 2 mM CaCl2, 1.3 mM MgCl2, 10 mM d-glucose, 100 U mL of penicillin, 100 pg mL of streptomycin, pH 7.3. 5. Surgical instruments for microdissection (scalpel, dissecting scissors, and needle probes). 6. Dissociation media aCSF containing high Mg2+ and low Ca2+ (26 mM NaHCO3, 124 mM NaCl, 5 mM KCl, 0.1 mMCaCl2, 3.2 mM...

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...

Behavioral Assessment

The most critical element in our place conditioning procedures is the use of an unbiased place conditioning apparatus. An unbiased apparatus is one in which the rats have no reliable a priori preference for any of the compartments, although it is important that each compartment have qualities that allow the animals to discriminate among environments. Our apparatus has three types of distinguishing features wall color (white and black), floor texture (rods and screen), and most importantly,...

Andrew D Medhurst and Menelas N Pangalos 1 Introduction

TaqMan reverse transcription-polymerase chain reaction (TaqMan RT-PCR) is a recently developed technique (1) that has been used to study gene expression in tissues of the central nervous system (CNS) including the striatum. For example, TaqMan has been used to profile mRNA distribution patterns across the brain for y-aminobutyric acid-B (GABAb) receptor subunits (2), 5-hydroxytryptamine4 (5-HT4) receptor splice variants (3), novel G-protein-coupled receptors (4), and ion channels including...

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...