Dopamine receptors: Molecular biology, biochemistry and behavioural aspects

Jackson, David M.; Westlind‐Danielsson, Anita

doi:10.1016/0163-7258(94)90041-8

Cited by 415 publications

(287 citation statements)

References 645 publications

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“…In brain, DA systems are involved in fundamental mechanisms related to behavioral adaptation (Le Moal and Simon, 1991;Jackson and Westlind-Danielsson, 1994). Dysfunction in pathways coordinating different DA terminal fields can lead to behavioral deficits that may be reflected in a variety of different psychiatric conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Dopamine (DA) is a well-recognized neurotransmitter within the central and peripheral nervous systems that exerts control over motor performance, emotion, motivation, cognition, and neuroendocrine responses (Le Moal and Simon, 1991;Jackson and Westlind-Danielsson, 1994). Alterations in dopaminergic function have been associated with several different neurological and psychiatric conditions that include Parkinson's and Huntington's diseases, schizophrenia, Tourette's syndrome, attention deficithyperactivity disorder (ADHD), and substance abuse (Carlsson, 1987).…”

Section: Introductionmentioning

confidence: 99%

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Novelty Seeking and Stereotypic Activation of Behavior in Mice with Disruption of the Dat1 Gene

Pogorelov

Rodriguiz

Insco

et al. 2005

Neuropsychopharmacol

137

116

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Disruption of the dopamine (DA) transporter (Dat1) gene in mice leads to a 50% reduction or complete elimination of Dat1 expression in striatum of respective heterozygous (HZ) and knockout (KO) mice. Compared to wild-type (WT) controls, extracellular DA is increased approximately two-and five-fold in the mutants. Although open field (OF) activity is similar for WT and HZ animals, it is enhanced for KO mice. The purpose of the present investigations was to study spontaneously emitted behaviors and to determine the behavioral and neurochemical mechanisms that may contribute to the hyperactivity of KO animals. Heterozygotes are less anxious than other genotypes and they engage in novelty-seeking behaviors that include increased time spent in the center of the OF, enhanced investigation of objects, and augmented free exploration of a novel environment. By comparison, KO mice display neophobia when initially exposed to novel conditions. Over time the anxiety-like response habituates and behaviors become activated and stereotyped; these responses are unrelated to exploration or novelty seeking. No alterations in extracellular DA levels or tissue contents from several brain regions are detected at the time of stereotypic activation of KO mice. By contrast, this behavior is accompanied by changes in serotonin metabolism in basal ganglia. This feature may contribute to the behavioral inflexibility of KO mice in different experimental contexts. Collectively, these findings suggest that disruption of the Dat1 gene in mice leads to two different phenotypes; one related to anxiety-reducing and novelty seeking, while the other has some homology to disorders with a stereotypical-perseverative spectrum.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novelty Seeking and Stereotypic Activation of Behavior in Mice with Disruption of the Dat1 Gene

Pogorelov

Rodriguiz

Insco

et al. 2005

Neuropsychopharmacol

137

116

View full text Add to dashboard Cite

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“…Both the stress‐treated MD and CUPS rats showed less exploratory interest, elevated DAT and DRD2‐4 levels, and reduced DRD1 level in the ST. As DRD2‐4 are inhibitory receptors and DRD1 is excitatory receptor (Jackson & Westlind‐Danielsson, 1994), the upregulation of DRD2‐4, DAT and the downregulation of DRD1 in the ST could synergically result in a decline in the activity of VTA‐ST neural pathway, which might finally lead to individual decreased exploratory interest. In contrast, the upregulation of excitatory DRD5 receptor in the ST of both MD‐ and CUPS‐treated rats might not be the direct effect of MD or CUPS, but might be the compensatory response toward the decreased activity of the VTA‐ST neural pathway.…”

Section: Discussionmentioning

confidence: 99%

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

et al. 2017

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BackgroundThe mesocorticolimbic dopamine system, which originates from the ventral tegmental area (VTA) and projects primarily to the prefrontal cortex (PFC), olfactory tubercle (OT), nucleus accumbens (NAc), dorsal striatum (ST), and the amygdala (AMy), plays a pivotal role in determining individual motivation and sensitivity to rewards, namely, anhedonia. Not all depressive individuals exhibited anhedonia, thus, it is natural to speculate that the heterogenous manifestations of depression might be related to the mesocorticolimbic dopamine system. Maternal deprivation (MD) and chronic unpredictable stress (CUPS) are two well‐established depressogenic stressors, and they were proven to induce different depressive phenotypes.MethodsThe depressive and anxiety‐like behaviors of MD and CUPS‐treated rats were measured by classical behavioral tests including open field, forced swimming, and sucrose preference test. The expression of D1‐5 dopamine receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system of rats exposed to MD and CUPS were measured by real‐time PCR and Western blot, respectively.ResultsSevere anhedonia was observed in MD but not CUPS rats. Divergent expression of D1 and D2 receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system were found between MD and CUPS rats. Significant correlations between different depressive behaviors and D1‐/D2‐like receptors and DAT protein levels in the mesocorticolimbic dopamine system were observed.ConclusionDifferent depressive behaviors of rats such as anhedonia, passive coping behavior, and declined exploratory interest might be related to divergent dopaminergic pathways. Anhedonia is associated with the dysfunction of VTA‐NAc and VTA‐OT dopaminergic pathways, the passive coping behavior is related to the dysregulation of VTA‐PFC and VTA‐AMy pathways, and individual exploratory interest is associated with abnormal activity of VTA‐PFC and VTA‐ST pathways.

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“…In the vertebrate nervous system the actions of dopamine are mediated by several pharmacologically distinct subclasses of G-protein-coupled receptors (Jackson and Westlind-Danielsson, 1994;O'Dowd et al, 1994). The general D1-like receptor subclass consists of the cloned receptor subtypes D1 and D5, whereas the D2-like receptor subclass consists of the cloned receptor subtypes, D2, D3, and D4 (Gingrich and C aron, 1993).…”

Section: Abstract: Cloned Dopamine Receptor; Drosophila Melanogastermentioning

confidence: 99%

“…The general D1-like receptor subclass consists of the cloned receptor subtypes D1 and D5, whereas the D2-like receptor subclass consists of the cloned receptor subtypes, D2, D3, and D4 (Gingrich and C aron, 1993). The D1-like receptors mediate their actions via an activation of adenylyl cyclase activity and phosphatidylinositol 4,5-bisphosphate (PI) metabolism, whereas the D2-like receptors inhibit adenylyl cyclase and activate potassium channels (Gingrich and Caron, 1993;Jackson and Westlind-Danielsson, 1994).…”

Section: Abstract: Cloned Dopamine Receptor; Drosophila Melanogastermentioning

confidence: 99%

Agonist-Specific Coupling of a ClonedDrosophila melanogasterD1-Like Dopamine Receptor to Multiple Second Messenger Pathways by Synthetic Agonists

et al. 1997

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The mechanism of coupling of a cloned Drosophila D1-like dopamine receptor, DopR99B, to multiple second messenger systems when expressed in Xenopus oocytes is described. The receptor is coupled directly to the generation of a rapid, transient intracellular Ca 2ϩ signal, monitored as changes in inward current mediated by the oocyte endogenous Ca 2ϩ -activated chloride channel, by a pertussis toxin-insensitive G-proteincoupled pathway. The more prolonged receptor-mediated changes in adenylyl cyclase activity are generated by an independent G-protein-coupled pathway that is pertussis toxinsensitive but calcium-independent, and G ␤␥ -subunits appear to be involved in the transduction of this response. This is the first evidence for the direct coupling of a cloned D1-like dopamine receptor both to the activation of adenylyl cyclase and to the initiation of an intracellular Ca 2ϩ signal. The pharmacological profile of both second messenger effects is identical for a range of naturally occurring catecholamine ligands (dopamine Ͼ norepinephrine Ͼ epinephrine) and for the blockade of dopamine responses by a range of synthetic antagonists. However, the pharmacological profiles of the two second messenger responses differ for a range of synthetic agonists. Thus, the receptor exhibits agonist-specific coupling to second messenger systems for synthetic agonists. This feature could provide a useful tool in the genetic analysis of the roles of the multiple second messenger pathways activated by this receptor, given the likely involvement of dopamine in the processes of learning and memory in the insect nervous system.

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Dopamine receptors: Molecular biology, biochemistry and behavioural aspects

Cited by 415 publications

References 645 publications

Novelty Seeking and Stereotypic Activation of Behavior in Mice with Disruption of the Dat1 Gene

Novelty Seeking and Stereotypic Activation of Behavior in Mice with Disruption of the Dat1 Gene

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

Agonist-Specific Coupling of a ClonedDrosophila melanogasterD1-Like Dopamine Receptor to Multiple Second Messenger Pathways by Synthetic Agonists

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