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Dopamine Pathway (dopamine + pathway)
Selected AbstractsAcute and long-term changes in the mesolimbic dopamine pathway after systemic or local single nicotine injectionsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002R. Ferrari Abstract We have examined several neurochemical and behavioural parameters related to the function of the mesolimbic dopamine (DA) pathway in animals treated with nicotine following three modes of drug administration, i.e. systemic intraperitoneal injection, intra-accumbens (Acb) infusion or intraventral tegmental area (intra-VTA) microinjection. The present modes of systemic, intra-Acb and intra-VTA nicotine administration elicited comparable acute increases in dialysate DA levels from the Acb. The increase in extracellular DA levels was paralleled by a significant enhancement of locomotion in a habituated environment in the case of systemic or intra-VTA nicotine administration, whereas unilateral or bilateral intra-Acb nicotine infusion was ineffective, showing that accumbal DA increase is not sufficient to elicit locomotion in this experimental paradigm. Intra-VTA, but not systemic or intra-Acb, nicotine administration caused a long-term (at least 24-h) increase in basal dialysate DA levels from the Acb. In addition, significant increases in tyrosine hydroxylase (TH) and GluR1 (but not dopamine transporter or NR1) mRNA levels in the VTA were detected 24 h after intra-VTA nicotine administration. Systemic nicotine injection caused only an increase in TH mRNA levels while intra-Acb infusion did not modify any of the mRNAs tested. The long-term increase in basal DA levels in the Acb and TH, and GluR1 mRNA levels in the VTA upon intra-VTA nicotine microinjection indicates that even a single nicotine injection can induce plastic changes of the mesolimbic DA pathway. [source] Regulation of axotomy-induced dopaminergic neuron death and c-Jun phosphorylation by targeted inhibition of cdc42 or mixed lineage kinaseJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Stephen J. Crocker Abstract Mechanical transection of the nigrostriatal dopamine pathway at the medial forebrain bundle (MFB) results in the delayed degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). We have previously demonstrated that c-Jun activation is an obligate component of neuronal death in this model. Here we identified the small GTPase, cdc42, and mixed lineage kinases (MLKs) as upstream factors regulating neuronal loss and activation of c-Jun following MFB axotomy. Adenovirus-mediated expression of a dominant-negative form of cdc42 in nigral neurons blocked MFB axotomy-induced activation (phosphorylation) of MAP kinase kinase 4 (MKK4) and c-Jun, resulting in attenuation of SNpc neuronal death. Pharmacological inhibition of MLKs, MKK4-activating kinases, significantly reduced the phosphorylation of c-Jun and abrogated dopaminergic neuronal degeneration following MFB axotomy. Taken together, these findings suggest that death of nigral dopaminergic neurons following axotomy can be attenuated by targeting cell signaling events upstream of c-Jun N-terminal mitogen-activated protein kinase/c-Jun. [source] Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson's disease through the IGF-I receptor signalling pathwayBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009Li Xu Background and purpose:, We have shown that ginsenoside Rg1 is a novel class of potent phytoestrogen and activates insulin-like growth factor-I receptor (IGF-IR) signalling pathway in human breast cancer MCF-7 cells. The present study tested the hypothesis that the neuroprotective actions of Rg1 involved activation of the IGF-IR signalling pathway in a rat model of Parkinson's disease, induced by 6-hydroxydopamine (6-OHDA). Experimental approach:, Ovariectomized rats were infused unilaterally with 6-OHDA into the medial forebrain bundle to lesion the nigrostriatal dopamine pathway and treated with Rg1 (1.5 h after 6-OHDA injections) in the absence or presence of the IGF-IR antagonist JB-1 (1 h before Rg1 injections). The rotational behaviour induced by apomorphine and the dopamine content in the striatum were studied. Protein and gene expression of tyrosine hydroxylase, dopamine transporter and Bcl-2 in the substantia nigra were also determined. Key results:, Rg1 treatment ameliorated the rotational behaviour induced by apomorphine in our model of nigrostriatal injury. This effect was partly blocked by JB-1. 6-OHDA significantly decreased the dopamine content of the striatum and treatment with Rg1 reversed this decrease. Treatment with Rg1 of 6-OHDA-lesioned rats reduced neurotoxicity, as measured by tyrosine hydroxylase, dopamine transporter and Bcl-2 protein and gene level in the substantia nigra. These effects were abolished by JB-1. Conclusions and implications:, These data provide the first evidence that Rg1 has neuroprotective effects on dopaminergic neurons in the 6-OHDA model of nigrostriatal injury and its actions might involve activation of the IGF-IR signalling pathway. [source] An investigation of associations between alcohol use disorder and polymorphisms on ALDH2, BDNF, 5-HTTLPR, and MTHFR genes in older Korean menINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2010Sangmoon Shin Abstract Background This study aimed to investigate the association of alcohol use disorder (AUD) with four candidate genes in older Korean men: aldehyde dehydrogenase 2 (ALDH2, 1/2), brain-derived neurotrophic factor (BDNF, val66met), serotonin transporter gene linked polymorphic region (5- HTTLPR, s/l), and methylenetetrahydrofolate reductase (MTHFR, c.677C,>,T). Methods A community sample of 300 men aged 65 or over were categorized into 68 subjects with AUD and 232 controls according to clinical examinations and DSM-IV criteria. Genotype distributions and allele frequencies were compared. Results Men with AUD had significantly higher ALDH2*1 and BDNF met allele frequencies compared to controls (p -values,<,0.05). No significant differences in genotype or allele frequencies were found for 5- HTTLPR or MTHFR (p -values,>,0.3). Conclusions AUD was associated with ALDH2*1 and BDNF met alleles in older Korean men. The first is consistent with previous research and likely to be explained by a protective effect of unpleasant symptoms following alcohol consumption associated with ALDH2*2. The second finding is novel and might be accounted for by BDNF -mediated serotonin or dopamine pathways. However, given the relatively small sample size, the results should be regarded as preliminary and requiring independent replication. Copyright © 2009 John Wiley & Sons, Ltd. [source] Dopamine and Oxytocin Interactions Underlying Behaviors: Potential Contributions to Behavioral DisordersCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 3 2010Tracey A. Baskerville Dopamine is an important neuromodulator that exerts widespread effects on the central nervous system (CNS) function. Disruption in dopaminergic neurotransmission can have profound effects on mood and behavior and as such is known to be implicated in various neuropsychiatric behavioral disorders including autism and depression. The subsequent effects on other neurocircuitries due to dysregulated dopamine function have yet to be fully explored. Due to the marked social deficits observed in psychiatric patients, the neuropeptide, oxytocin is emerging as one particular neural substrate that may be influenced by the altered dopamine levels subserving neuropathologic-related behavioral diseases. Oxytocin has a substantial role in social attachment, affiliation and sexual behavior. More recently, it has emerged that disturbances in peripheral and central oxytocin levels have been detected in some patients with dopamine-dependent disorders. Thus, oxytocin is proposed to be a key neural substrate that interacts with central dopamine systems. In addition to psychosocial improvement, oxytocin has recently been implicated in mediating mesolimbic dopamine pathways during drug addiction and withdrawal. This bi-directional role of dopamine has also been implicated during some components of sexual behavior. This review will discuss evidence for the existence dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression. Preliminary findings suggest that whilst further rigorous testing has to be conducted to establish a dopamine/oxytocin link in human disorders, animal models seem to indicate the existence of broad and integrated brain circuits where dopamine and oxytocin interactions at least in part mediate socio-affiliative behaviors. A profound disruption to these pathways is likely to underpin associated behavioral disorders. Central oxytocin pathways may serve as a potential therapeutic target to improve mood and socio-affiliative behaviors in patients with profound social deficits and/or drug addiction. [source] | |||||||||||||