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Nicotine or cocaine, when administered intravenously, induces an increase of extracellular dopamine in the nucleus accumbens. The nicotine-mediated increase was shown to occur at least in part through increase of the activity of dopamine neurons in the ventral tegmental area. As part of our continuing studies of the mechanisms of nicotine effects in the(More)
One of the significant factors that affect brain dopamine function is the activity of tyrosine hydroxylase (TH), the first and rate-limiting enzyme in catecholamine biosynthesis. For the analysis of the genetically determined role of dopamine function and TH in behavior and in the regulatory mechanisms of the mesotelencephalic dopamine system we devised a(More)
1Laboratory of Neurobehavioral Genetics, Nathan S. K1ine Institute, 140 Old Orangeburg Road, Orangeburg, New York 10962 2Department of Psychiatry, New York University Medical Center, 550 First Avenue, New York, New York 10016 3Research Genetics, 2130 Memorial Parkway, S.W., Huntsville, Alabama 35801 4Unit on Neurotoxicology & Neuroprotection, Laboratory of(More)
The ability of 1-deprenyl to protect against the parkinsonian effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been attributed to the inhibition of conversion of MPTP to MPP+ (1-methyl-4-phenylpyridinium) catalyzed by MAO-B. We report here that deprenyl-treatment in mice has an additional neuroprotective element associated with the rapid(More)
Familial Parkinson’s disease (PD) has been linked to point mutations and duplication of the α-synuclein gene and mutant α-synuclein expression increases the vulnerability of neurons to exogenous insults. In this study, we analyzed the levels of dopamine and its metabolites in the olfactory bulb (OB), and nigrostriatal regions of transgenic mice expressing(More)
Studies have shown a greater preference for the self-administration of drugs such as nicotine and cocaine in the Lewis rat strain than in the Fischer 344 strain. We examined some factors that could contribute to such a difference. The baseline level of extracellular dopamine in nucleus accumbens shell was about 3-times higher in Fischer rats than in Lewis(More)
Cotinine is the major metabolite of nicotine. Nicotine is rapidly metabolized and has a short half-life, but cotinine is metabolized and eliminated at a much lower rate. Because of the resulting increase with time in the cotinine to nicotine ratio in the body, including in the brain, it is of interest to examine the effect of cotinine on nicotine-induced(More)
The effect of an individual locus that affects complex traits is difficult to detect because it is responsible for only a fraction of the total environmental, genetic, and interaction variation, and its contribution is therefore usually masked. In 1983, to diminish the above-mentioned difficulties, we began the development of a novel approach to QTL(More)
This study provides evidence that quinidine can be used as a probe substrate for ABCB1 in multiple experimental systems both in vitro and in vivo relevant to the blood-brain barrier (BBB). The combination of quinidine and PSC-833 (valspodar) is an effective tool to assess investigational drugs for interactions on ABCB1. Effects of quinidine and(More)