Dopamine beta-hydroxylase knockout mice have alterations in dopamine signaling and are hypersensitive to cocaine. Export

@article{citeulike:769021, abstract = {Multiple lines of evidence demonstrate that the noradrenergic system provides both direct and indirect excitatory drive onto midbrain dopamine (DA) neurons. We used DA beta-hydroxylase (DBH) knockout (Dbh-/-) mice that lack norepinephrine (NE) to determine the consequences of chronic NE deficiency on midbrain DA neuron function in vivo. Basal extracellular DA levels were significantly attenuated in the nucleus accumbens (NAc) and caudate putamen (CP), but not prefrontal cortex (PFC), of Dbh-/- mice, while amphetamine-induced DA release was absent in the NAc and attenuated in the CP and PFC. The decrease in dopaminergic tone was associated with a profound increase in the density of high-affinity state D1 and D2 DA receptors in the NAc and CP, while DA receptors in the PFC were relatively unaffected. As a behavioral consequence of these neurochemical changes, Dbh-/- mice were hypersensitive to the psychomotor, rewarding, and aversive effects of cocaine, as measured by locomotor activity and conditioned place preference. Antagonists of DA, but not 5-HT, receptors attenuated the locomotor hypersensitivity to cocaine in Dbh-/- mice. As DBH activity in humans is genetically controlled and the DBH inhibitor disulfiram has shown promise as a pharmacotherapy for cocaine dependence, these results have implications for the influence of genetic and pharmacological DBH inhibition on DA system function and drug addiction.}, author = {Schank, Jesse R. and Ventura, Rossella and Puglisi-Allegra, Stefano and Alcaro, Antonio and Cole, Charlene D. and Liles, L. Cameron and Seeman, Philip and Weinshenker, David}, citeulike-article-id = {769021}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/sj.npp.1301000}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16395294}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16395294}, doi = {10.1038/sj.npp.1301000}, issn = {0893-133X}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, keywords = {dbh\_ko, dbh\_nr1\_paper, dopamine, noradrenaline, noradrenergic}, month = {October}, number = {10}, pages = {2221--2230}, posted-at = {2009-08-19 16:32:41}, priority = {5}, publisher = {Nature Publishing Group}, title = {Dopamine beta-hydroxylase knockout mice have alterations in dopamine signaling and are hypersensitive to cocaine.}, url = {http://dx.doi.org/10.1038/sj.npp.1301000}, volume = {31}, year = {2006} }

TY - JOUR ID - citeulike:769021 L3 - citeulike-article-id:769021 N2 - Multiple lines of evidence demonstrate that the noradrenergic system provides both direct and indirect excitatory drive onto midbrain dopamine (DA) neurons. We used DA beta-hydroxylase (DBH) knockout (Dbh-/-) mice that lack norepinephrine (NE) to determine the consequences of chronic NE deficiency on midbrain DA neuron function in vivo. Basal extracellular DA levels were significantly attenuated in the nucleus accumbens (NAc) and caudate putamen (CP), but not prefrontal cortex (PFC), of Dbh-/- mice, while amphetamine-induced DA release was absent in the NAc and attenuated in the CP and PFC. The decrease in dopaminergic tone was associated with a profound increase in the density of high-affinity state D1 and D2 DA receptors in the NAc and CP, while DA receptors in the PFC were relatively unaffected. As a behavioral consequence of these neurochemical changes, Dbh-/- mice were hypersensitive to the psychomotor, rewarding, and aversive effects of cocaine, as measured by locomotor activity and conditioned place preference. Antagonists of DA, but not 5-HT, receptors attenuated the locomotor hypersensitivity to cocaine in Dbh-/- mice. As DBH activity in humans is genetically controlled and the DBH inhibitor disulfiram has shown promise as a pharmacotherapy for cocaine dependence, these results have implications for the influence of genetic and pharmacological DBH inhibition on DA system function and drug addiction. IS - 10 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology SN - 0893-133X EP - 2230 TI - Dopamine beta-hydroxylase knockout mice have alterations in dopamine signaling and are hypersensitive to cocaine. PB - Nature Publishing Group VL - 31 SP - 2221 KW - dbh_ko KW - dbh_nr1_paper KW - dopamine KW - noradrenaline KW - noradrenergic AU - Schank, Jesse AU - Ventura, Rossella AU - Puglisi-Allegra, Stefano AU - Alcaro, Antonio AU - Cole, Charlene AU - Liles, Cameron AU - Seeman, Philip AU - Weinshenker, David PY - 2006/10// UR - http://dx.doi.org/10.1038/sj.npp.1301000 ER -