Dopamine implications

The symptoms of parkinsonism are caused by a depletion of dopamine in the CNS. Dopamine, when given orally, does not cross the blood-brain barrier and therefore is ineffective The body s blood-brain barrier is a mesh-work of tightly packed cells in die walls of the brain s capillaries that screen out certain substances. This unique meshwork of cells in the CNS prohibits large and potentially harmful molecules from crossing into die brain. This ability to screen out certain substances lias important implications for drug dierapy because some drugs are able to pass through die blood-brain barrier more easily dian odiers. 

Yokel, R.A., and Wise, R.A. Increased lever pressing for amphetamine after pimozide in rats Implications for a dopamine theory of reward. Science 187 547-549, 1975. 

Kish, S.J. Shannak, K. and Homykiewicz, O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson s disease. Pathophysiologic and clinical implications. N Engl J Med 318 876-880, 1988. 

The neurotoxic effects of all these compounds are antagonized by inhibitors of monoamine uptake (table 1), implicating the membrane uptake carrier on serotonin and dopamine neurons in the mechanism of neurotoxicity. In this regard, these amphetamines are like a drug somewhat related in structure, namely l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP), a Parkinsonism-causing neurotoxic dmg that has been studied intensely since 1983 (Langston and Irwin 1986). In the case of MPTP, the mechanism by which inhibitors of the dopamine uptake carrier block the neurotoxicity toward dopamine neurons (mainly nigrostriatal dopamine neurons) seems clear. A metabolite of MPTP, l-methyl-4-phenylpyridinium (MPP-I-), has been shown to be a substrate for the dopamine uptake carrier (Javitch et al. 1985). Thus accumulation of MPP-I-, formed metabolically from... 

The exact cause of attention-deficit hyperactivity disorder is unknown, but dysfunction in neurotransmitters norepinephrine and dopamine has been implicated as a key component. 

The main mechanism of action of caffeine occurs via the blockade of adenosine receptors in the CNS. Adenosine is an autacoid, which is involved in the modulation of behavior, oxygenation of cells, and dilatation of cerebral and coronary blood vessels and indirectly inhibits the release of dopamine. The blockade of adenosine receptors by caffeine increases the activity of dopamine, which is implicated in the effects of caffeine (91). The question that arises from this observation is to know whether or not adenosine antagonists hold potential for the treatment of Parkinsonism, and further study on the adenosine receptor antagonists from medicinal plants should be encouraged. A possible source for such agents could be the medicinal flora of Asia and the Pacific, among which is the family Sapindaceae. 

Svingos, A.L., Clarke, C.L., and Pickel, V.M., Localization of delta-opioid receptor and dopamine transporter in the nucleus accumbens shell implications for opiate and psychostimulant cross sensitization, Synapse, 34, 1, 1999. 

Zetterstrom, T., Sharp, T., Collin, A.K., Ungerstedt, U. In vivo measurement of extracellular dopamine and DOPAC in rat striatum after various dopamine-releasing drugs implications for the origin of extracellular DOPAC. Eur. J. Pharmacol. 148 327, 1988. 

Neisewander J.L., Fuchs R.A., Tran-Nguyen L.T., Weber S.M., Coffey G.P., Joyce J.N. Increases in dopamine D3 receptor binding in rats receiving a cocaine challenge at various time points after cocaine self-administration implications for cocaine-seeking behavior. Neuropsychopharmacology. 29 1479, 2004. 

Gudelsky, G.A. and Nash, J.F., Carrier-mediated release of serotonin by 3,4-methylenedioxymethamphetamine implications for serotonin-dopamine interactions, J. Neurochem. 66(1), 243-249, 1996. 

Another crucial problem for any neurochemical model is cause and effect. Neuroleptics have a high affinity for dopamine receptors, particularly the D2-subtype. There is also a highly significant positive correlation (r > +0.9) between this receptor binding and their clinical potency (Seeman, 1980). But, this does not necessarily implicate elevated dopamine levels as the cause of schizophrenia. Moreover, blockade of dopamine receptors happens very rapidly, whereas clinical benefits are only seen after chronic treatment. Rose (1973) has criticised the reductionist statement that an abnormal biochemistry causes schizophrenia because it relates cause and effect at different organisational levels (namely, the molecular and behavioural). But, while it can be legitimate to discuss cause and effect at the same level that chlorpromazine blocks dopamine receptors (one molecule altering the response of another), it is not valid to infer that increased dopamine activity causes schizophrenia. Put another way ... 

Muscarinic and dopaminergic pathways in the CNS interact in control of numerous pathways implicated in diseases, especially those controlling involuntary motor systems. Muscarinic effects on dopamine release are mediated in several ways via different mAChR subtypes. Thus mAChR facilitation of DA release appears to involve M4 receptors on GABA projection neurons to the striatum, while M3 receptors on striatal DA neurons are predicted to inhibit striatal DA release [12],... 

Sesack, S. R. and Carr, D. B. Selective prefrontal cortex inputs to dopamine cells implications for schizophrenia. Physiol. Behav. 77 513-517,2002. 

A2A receptors and dopamine D2 receptors in the ventral striopalhdal system. Implications for the treatment of schizophrenia. Neuroscience 63 765-773,1994. 

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