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Attention-deficit-hyperactivity disorder and reward deficiency syndrome.

Blum K, Chen AL, Braverman ER, Comings DE, Chen TJ, Arcuri V, Blum SH, Downs BW, Waite RL, Notaro A, Lubar J, Williams L, Prihoda TJ, Palomo T, Oscar-Berman M - Neuropsychiatr Dis Treat (2008)

Bottom Line: Moreover, this genetic trait is due in part to a form of a gene (DRD(2) A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites.This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities.Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. drd2gene@aol.com

ABSTRACT
Molecular genetic studies have identified several genes that may mediate susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of the literature suggests that when there is a dysfunction in the "brain reward cascade," especially in the dopamine system, causing a low or hypo-dopaminergic trait, the brain may require dopamine for individuals to avoid unpleasant feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors, because the drugs activate release of dopamine, which can diminish abnormal cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD(2) A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other "reward genes" are important common determinants of reward deficiency syndrome (RDS), which we hypothesize includes ADHD as a behavioral subtype. We further hypothesize that early diagnosis through genetic polymorphic identification in combination with DNA-based customized nutraceutical administration to young children may attenuate behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.

No MeSH data available.


Related in: MedlinePlus

Interactions in brain reward regions. (1) Serotonin in the hypothalamus indirectly activates opiate receptors and causes a release of enkephalins in the ventral tegmental region A10. The enkephalins inhibit the firing of GABA, which originates in the substantia nigra A9 region. (2) GABA’s normal role, acting through GABA B receptors, is to inhibit and control the amount of dopamine released at the ventral tegmental regions for action at the nucleus accumbens. When dopamine is released in the nucleus accumbens, it activates dopamine D2 receptors, a key reward site. This release is also regulated by enkephalins acting through GABA. The supply of enkephalins is controlled by the amount of the neuropeptidases that destroy them. (3) Dopamine also may be released into the amygdala. From the amygdala, dopamine stimulates the hippocampus and the CA and cluster cells stimulate dopamine D2 receptors. (4) An alternate pathway involves norepinephrine in the locus ceruleus whose fibers project into the hippocampus at a reward area centering around cluster cells that have not been precisely identified, but which have been designated as CAx. When GABA A receptors in the hippocampus are stimulated, they cause the release of norepinephrine.
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f1-ndt-4-893: Interactions in brain reward regions. (1) Serotonin in the hypothalamus indirectly activates opiate receptors and causes a release of enkephalins in the ventral tegmental region A10. The enkephalins inhibit the firing of GABA, which originates in the substantia nigra A9 region. (2) GABA’s normal role, acting through GABA B receptors, is to inhibit and control the amount of dopamine released at the ventral tegmental regions for action at the nucleus accumbens. When dopamine is released in the nucleus accumbens, it activates dopamine D2 receptors, a key reward site. This release is also regulated by enkephalins acting through GABA. The supply of enkephalins is controlled by the amount of the neuropeptidases that destroy them. (3) Dopamine also may be released into the amygdala. From the amygdala, dopamine stimulates the hippocampus and the CA and cluster cells stimulate dopamine D2 receptors. (4) An alternate pathway involves norepinephrine in the locus ceruleus whose fibers project into the hippocampus at a reward area centering around cluster cells that have not been precisely identified, but which have been designated as CAx. When GABA A receptors in the hippocampus are stimulated, they cause the release of norepinephrine.

Mentions: As can be seen in Figure 1, the following interactions take place in brain reward areas (Blum and Payne 1991; Stein and Belluzzi 1986): (1) Serotonin in the hypothalamus indirectly activates opiate receptors and causes a release of enkephalins in the ventral tegmental region A10. The enkephalins inhibit the firing of gamma-aminobutyric acid neurotransmitter (GABA), which originates in the substantia nigra A9 region. (2) GABA’s normal role, acting through GABA B receptors, is to inhibit and control the amount of dopamine released at the ventral tegmental regions for action at the nucleus accumbens. When dopamine is released in the nucleus accumbens, it activates dopamine D2 receptors. This release also is regulated by enkephalins acting through GABA. The supply of enkephalins is controlled by the amount of the neuropeptidases, which destroy them. (3) Dopamine also may be released into the amygdala. From the amygdala, dopamine exerts an effect on neurons within the hippocampus. (4) An alternate pathway involves norepinephrine in the locus ceruleus whose fibers project into the hippocampus at a reward area centering around cluster cells, which have not been precisely identified (designated as CAx). When GABA A receptors in the hippocampus are stimulated, they cause the release of norepinephrine.


Attention-deficit-hyperactivity disorder and reward deficiency syndrome.

Blum K, Chen AL, Braverman ER, Comings DE, Chen TJ, Arcuri V, Blum SH, Downs BW, Waite RL, Notaro A, Lubar J, Williams L, Prihoda TJ, Palomo T, Oscar-Berman M - Neuropsychiatr Dis Treat (2008)

Interactions in brain reward regions. (1) Serotonin in the hypothalamus indirectly activates opiate receptors and causes a release of enkephalins in the ventral tegmental region A10. The enkephalins inhibit the firing of GABA, which originates in the substantia nigra A9 region. (2) GABA’s normal role, acting through GABA B receptors, is to inhibit and control the amount of dopamine released at the ventral tegmental regions for action at the nucleus accumbens. When dopamine is released in the nucleus accumbens, it activates dopamine D2 receptors, a key reward site. This release is also regulated by enkephalins acting through GABA. The supply of enkephalins is controlled by the amount of the neuropeptidases that destroy them. (3) Dopamine also may be released into the amygdala. From the amygdala, dopamine stimulates the hippocampus and the CA and cluster cells stimulate dopamine D2 receptors. (4) An alternate pathway involves norepinephrine in the locus ceruleus whose fibers project into the hippocampus at a reward area centering around cluster cells that have not been precisely identified, but which have been designated as CAx. When GABA A receptors in the hippocampus are stimulated, they cause the release of norepinephrine.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2626918&req=5

f1-ndt-4-893: Interactions in brain reward regions. (1) Serotonin in the hypothalamus indirectly activates opiate receptors and causes a release of enkephalins in the ventral tegmental region A10. The enkephalins inhibit the firing of GABA, which originates in the substantia nigra A9 region. (2) GABA’s normal role, acting through GABA B receptors, is to inhibit and control the amount of dopamine released at the ventral tegmental regions for action at the nucleus accumbens. When dopamine is released in the nucleus accumbens, it activates dopamine D2 receptors, a key reward site. This release is also regulated by enkephalins acting through GABA. The supply of enkephalins is controlled by the amount of the neuropeptidases that destroy them. (3) Dopamine also may be released into the amygdala. From the amygdala, dopamine stimulates the hippocampus and the CA and cluster cells stimulate dopamine D2 receptors. (4) An alternate pathway involves norepinephrine in the locus ceruleus whose fibers project into the hippocampus at a reward area centering around cluster cells that have not been precisely identified, but which have been designated as CAx. When GABA A receptors in the hippocampus are stimulated, they cause the release of norepinephrine.
Mentions: As can be seen in Figure 1, the following interactions take place in brain reward areas (Blum and Payne 1991; Stein and Belluzzi 1986): (1) Serotonin in the hypothalamus indirectly activates opiate receptors and causes a release of enkephalins in the ventral tegmental region A10. The enkephalins inhibit the firing of gamma-aminobutyric acid neurotransmitter (GABA), which originates in the substantia nigra A9 region. (2) GABA’s normal role, acting through GABA B receptors, is to inhibit and control the amount of dopamine released at the ventral tegmental regions for action at the nucleus accumbens. When dopamine is released in the nucleus accumbens, it activates dopamine D2 receptors. This release also is regulated by enkephalins acting through GABA. The supply of enkephalins is controlled by the amount of the neuropeptidases, which destroy them. (3) Dopamine also may be released into the amygdala. From the amygdala, dopamine exerts an effect on neurons within the hippocampus. (4) An alternate pathway involves norepinephrine in the locus ceruleus whose fibers project into the hippocampus at a reward area centering around cluster cells, which have not been precisely identified (designated as CAx). When GABA A receptors in the hippocampus are stimulated, they cause the release of norepinephrine.

Bottom Line: Moreover, this genetic trait is due in part to a form of a gene (DRD(2) A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites.This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities.Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. drd2gene@aol.com

ABSTRACT
Molecular genetic studies have identified several genes that may mediate susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of the literature suggests that when there is a dysfunction in the "brain reward cascade," especially in the dopamine system, causing a low or hypo-dopaminergic trait, the brain may require dopamine for individuals to avoid unpleasant feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors, because the drugs activate release of dopamine, which can diminish abnormal cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD(2) A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other "reward genes" are important common determinants of reward deficiency syndrome (RDS), which we hypothesize includes ADHD as a behavioral subtype. We further hypothesize that early diagnosis through genetic polymorphic identification in combination with DNA-based customized nutraceutical administration to young children may attenuate behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.

No MeSH data available.


Related in: MedlinePlus