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      The Dopaminergic System in Peripheral Blood Lymphocytes: From Physiology to Pharmacology and Potential Applications to Neuropsychiatric Disorders

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          Abstract

          Besides its action on the nervous system, dopamine (DA) plays a role on neural-immune interactions. Here we review the current evidence on the dopaminergic system in human peripheral blood lymphocytes (PBL). PBL synthesize DA through the tyrosine-hydroxylase/DOPA-decarboxylase pathway, and express DA receptors and DA transporter (DAT) on their plasma membrane. Stimulation of DA receptors on PBL membrane contributes to modulate the development and initiation of immune responses under physiological conditions and in immune system pathologies such as autoimmunity or immunodeficiency.

          The characterization of DA system in PBL gave rise to a further line of research investigating the feasibility of PBL as a cellular model for studying DA derangement in neuropsychiatric disorders. Several reports showed changes of the expression of DAT and/or DA receptors in PBL from patients suffering from several neuropsychiatric disorders, in particular parkinsonian syndromes, schizophrenia and drug- or alcohol-abuse. Despite some methodological and theoretical limitations, these findings suggest that PBL may prove a cellular tool with which to identify the derangement of DA transmission in neuropsychiatric diseases, as well as to monitor the effects of pharmacological treatments.

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          Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

          A J Hughes, S Daniel, L Kilford … (1992)
          Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.
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            Imaging dopamine's role in drug abuse and addiction.

            N D Volkow, J Fowler, G. J. Wang … (2009)
            Dopamine is involved in drug reinforcement but its role in addiction is less clear. Here we describe PET imaging studies that investigate dopamine's involvement in drug abuse in the human brain. In humans the reinforcing effects of drugs are associated with large and fast increases in extracellular dopamine, which mimic those induced by physiological dopamine cell firing but are more intense and protracted. Since dopamine cells fire in response to salient stimuli, supraphysiological activation by drugs is experienced as highly salient (driving attention, arousal, conditioned learning and motivation) and with repeated drug use may raise the thresholds required for dopamine cell activation and signaling. Indeed, imaging studies show that drug abusers have marked decreases in dopamine D2 receptors and in dopamine release. This decrease in dopamine function is associated with reduced regional activity in orbitofrontal cortex (involved in salience attribution; its disruption results in compulsive behaviors), cingulate gyrus (involved in inhibitory control; its disruption results in impulsivity) and dorsolateral prefrontal cortex (involved in executive function; its disruption results in impaired regulation of intentional actions). In parallel, conditioning triggered by drugs leads to enhanced dopamine signaling when exposed to conditioned cues, which then drives the motivation to procure the drug in part by activation of prefrontal and striatal regions. These findings implicate deficits in dopamine activity-inked with prefrontal and striatal deregulation-in the loss of control and compulsive drug intake that results when the addicted person takes the drugs or is exposed to conditioned cues. The decreased dopamine function in addicted individuals also reduces their sensitivity to natural reinforcers. Therapeutic interventions aimed at restoring brain dopaminergic tone and activity of cortical projection regions could improve prefrontal function, enhance inhibitory control and interfere with impulsivity and compulsive drug administration while helping to motivate the addicted person to engage in non-drug related behaviors.
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              Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism.

              Gianluigi Tanda, Francesco Pontieri, Gaetano Di Chiara (1997)
              The effects of the active ingredient of Cannabis, Delta9-tetrahydrocannabinol (Delta9-THC), and of the highly addictive drug heroin on in vivo dopamine transmission in the nucleus accumbens were compared in Sprague-Dawley rats by brain microdialysis. Delta9-THC and heroin increased extracellular dopamine concentrations selectively in the shell of the nucleus accumbens; these effects were mimicked by the synthetic cannabinoid agonist WIN55212-2. SR141716A, an antagonist of central cannabinoid receptors, prevented the effects of Delta9-THC but not those of heroin. Naloxone, a generic opioid antagonist, administered systemically, or naloxonazine, an antagonist of micro1 opioid receptors, infused into the ventral tegmentum, prevented the action of cannabinoids and heroin on dopamine transmission. Thus, Delta9-THC and heroin exert similar effects on mesolimbic dopamine transmission through a common mu1 opioid receptor mechanism located in the ventral mesencephalic tegmentum.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Curr Neuropharmacol
                Journal ID (publisher-id): CN
                Title: Current Neuropharmacology
                Publisher: Bentham Science Publishers Ltd
                ISSN (Print): 1570-159X
                ISSN (Electronic): 1875-6190
                Publication date (Print): June 2011
                Volume: 9
                Issue: 2
                Pages: 278-288
                Affiliations
                [1 ]Department of Neurology and Psychiatry, “Sapienza” University
                [2 ]Movement Disorder Unit, “Sant'Andrea” Hospital, Rome, Italy
                Author notes
                [* ]Address correspondence to this author at the Department of Neurology and Psychiatry, “Sapienza” University. Via di Grottarossa, 1035 – 00189 Rome, Italy; Tel: (+39) 06 33775579; Fax: (+39) 06 33775900; E-mail: fe.pontieri@ 123456gmail.com
                Article
                Publisher ID: CN-9-278
                DOI: 10.2174/157015911795596612
                PMC ID: 3131719
                PubMed ID: 22131937
                SO-VID: 64fb180c-90c3-41ff-8a41-30e35c8dc8b5
                Copyright © ©2011 Bentham Science Publishers Ltd
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 30 April 2010
                Date revision received : 17 September 2010
                Date accepted : 24 September 2010
                Categories
                Subject: Article

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: dopamine,dopamine receptors,neuropsychiatric disorders,dopamine transporter,peripheral blood lymphocytes.
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: dopamine, dopamine receptors, neuropsychiatric disorders, dopamine transporter, peripheral blood lymphocytes.

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