FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2136812067> ?p ?o ?g. }

• W2136812067 endingPage "196" @default.
• W2136812067 startingPage "176" @default.
• W2136812067 abstract "It is well known that after prolonged abstinence, individuals who use their drug of choice experience a powerful euphoria that often precipitates relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed supersensitivity might be tied to genetic dopaminergic polymorphisms. Another therapeutic conundrum relates to the paradoxical finding that the dopaminergic agonist bromocriptine induces stronger activation of brain reward circuitry in individuals who carry the DRD2 A1 allele compared with DRD2 A2 allele carriers. Because carriers of the A1 allele relative to the A2 allele of the DRD2 gene have significantly lower D2 receptor density, a reduced sensitivity to dopamine agonist activity would be expected in the former. Thus, it is perplexing that with low D2 density there is an increase in reward sensitivity with the dopamine D2 agonist bromocriptine. Moreover, under chronic or long-term therapy with D2 agonists, such as bromocriptine, it has been shown in vitro that there is a proliferation of D2 receptors. One explanation for this relates to the demonstration that the A1 allele of the DRD2 gene is associated with increased striatal activity of L-amino acid decarboxylase, the final step in the biosynthesis of dopamine. This appears to be a protective mechanism against low receptor density and would favor the utilization of an amino acid neurotransmitter precursor like L-tyrosine for preferential synthesis of dopamine. This seems to lead to receptor proliferation to normal levels and results in significantly better treatment compliance only in A1 carriers.We propose that low D2 receptor density and polymorphisms of the D2 gene are associated with risk for relapse of substance abuse, including alcohol dependence, heroin craving, cocaine dependence, methamphetamine abuse, nicotine sensitization, and glucose craving. With this in mind, we suggest a putative physiological mechanism that may help to explain the enhanced sensitivity following intense acute dopaminergic D2 receptor activation: denervation supersensitivity. Rats with unilateral depletions of neostriatal dopamine display increased sensitivity to dopamine agonists estimated to be 30 to 100 x in the 6-hydroxydopamine (6-OHDA) rotational model. Given that mild striatal dopamine D2 receptor proliferation occurs (20%-40%), it is difficult to explain the extent of behavioral supersensitivity by a simple increase in receptor density. Thus, the administration of dopamine D2 agonists would target D2 sensitization and attenuate relapse, especially in D2 receptor A1 allele carriers. This hypothesized mechanism is supported by clinical trials utilizing amino acid neurotransmitter precursors, enkephalinase, and catechol-O-methyltransferase (COMT) enzyme inhibition, which have resulted in attenuated relapse rates in reward deficiency syndrome (RDS) probands. If future translational research reveals that dopamine agonist therapy reduces relapse in RDS, it would support the proposed concept, which we term deprivation-amplification relapse therapy (DART). This term couples the mechanism for relapse, which is deprivation-amplification, especially in DRD2 A1 allele carriers with natural D2 agonist therapy utilizing amino acid precursors and COMT and enkepalinase inhibition therapy." @default.
• W2136812067 created "2016-06-24" @default.
• W2136812067 creator A5002463971 @default.
• W2136812067 creator A5017907782 @default.
• W2136812067 creator A5031879672 @default.
• W2136812067 creator A5033241034 @default.
• W2136812067 creator A5042753204 @default.
• W2136812067 creator A5048489111 @default.
• W2136812067 creator A5056618455 @default.
• W2136812067 creator A5060614877 @default.
• W2136812067 creator A5063168541 @default.
• W2136812067 creator A5067927137 @default.
• W2136812067 creator A5068209735 @default.
• W2136812067 creator A5068786123 @default.
• W2136812067 creator A5077020871 @default.
• W2136812067 date "2009-11-01" @default.
• W2136812067 modified "2023-10-16" @default.
• W2136812067 title "Neurogenetics of Dopaminergic Receptor Supersensitivity in Activation of Brain Reward Circuitry and Relapse: Proposing “Deprivation-Amplification Relapse Therapy” (DART)" @default.
• W2136812067 cites W1492673141 @default.
• W2136812067 cites W1512774816 @default.
• W2136812067 cites W1568198343 @default.
• W2136812067 cites W1569364613 @default.
• W2136812067 cites W1579518684 @default.
• W2136812067 cites W1601690727 @default.
• W2136812067 cites W1768956672 @default.
• W2136812067 cites W1846887479 @default.
• W2136812067 cites W1913794139 @default.
• W2136812067 cites W1920680810 @default.
• W2136812067 cites W1964392085 @default.
• W2136812067 cites W1965792012 @default.
• W2136812067 cites W1965904098 @default.
• W2136812067 cites W1966864307 @default.
• W2136812067 cites W1968449546 @default.
• W2136812067 cites W1969163064 @default.
• W2136812067 cites W1969351952 @default.
• W2136812067 cites W1971192317 @default.
• W2136812067 cites W1971498141 @default.
• W2136812067 cites W1972667140 @default.
• W2136812067 cites W1973464479 @default.
• W2136812067 cites W1977102147 @default.
• W2136812067 cites W1977192770 @default.
• W2136812067 cites W1977460718 @default.
• W2136812067 cites W1977672139 @default.
• W2136812067 cites W1977693441 @default.
• W2136812067 cites W1977918460 @default.
• W2136812067 cites W1978027318 @default.
• W2136812067 cites W1978453350 @default.
• W2136812067 cites W1978726368 @default.
• W2136812067 cites W1978812567 @default.
• W2136812067 cites W1979466796 @default.
• W2136812067 cites W1980233933 @default.
• W2136812067 cites W1980890656 @default.
• W2136812067 cites W1981102082 @default.
• W2136812067 cites W1981283994 @default.
• W2136812067 cites W1981539473 @default.
• W2136812067 cites W1982411078 @default.
• W2136812067 cites W1982502538 @default.
• W2136812067 cites W1982707902 @default.
• W2136812067 cites W1984247449 @default.
• W2136812067 cites W1984296918 @default.
• W2136812067 cites W1984346427 @default.
• W2136812067 cites W1984460640 @default.
• W2136812067 cites W1986331833 @default.
• W2136812067 cites W1986632570 @default.
• W2136812067 cites W1988370882 @default.
• W2136812067 cites W1988560875 @default.
• W2136812067 cites W1988916326 @default.
• W2136812067 cites W1989416066 @default.
• W2136812067 cites W1989650181 @default.
• W2136812067 cites W1990490435 @default.
• W2136812067 cites W1990772702 @default.
• W2136812067 cites W1991448902 @default.
• W2136812067 cites W1993354858 @default.
• W2136812067 cites W1993691356 @default.
• W2136812067 cites W1996124584 @default.
• W2136812067 cites W1998033984 @default.
• W2136812067 cites W1998618539 @default.
• W2136812067 cites W1999435825 @default.
• W2136812067 cites W2000104036 @default.
• W2136812067 cites W2001274027 @default.
• W2136812067 cites W2001941840 @default.
• W2136812067 cites W2002482831 @default.
• W2136812067 cites W2004650335 @default.
• W2136812067 cites W2004676994 @default.
• W2136812067 cites W2005239439 @default.
• W2136812067 cites W2005509461 @default.
• W2136812067 cites W2006850368 @default.
• W2136812067 cites W2009784590 @default.
• W2136812067 cites W2012314921 @default.
• W2136812067 cites W2012329898 @default.
• W2136812067 cites W2012618914 @default.
• W2136812067 cites W2013145111 @default.
• W2136812067 cites W2013791616 @default.
• W2136812067 cites W2013918323 @default.
• W2136812067 cites W2014479855 @default.
• W2136812067 cites W2015421768 @default.
• W2136812067 cites W2015735605 @default.
• W2136812067 cites W2016232482 @default.

• next