Genetic variants of dopamine D2 receptor impact heterodimerization with dopamine D1 receptor

2017 ◽  
Vol 69 (2) ◽  
pp. 235-241 ◽  
Author(s):  
Ewa Błasiak ◽  
Sylwia Łukasiewicz ◽  
Kinga Szafran-Pilch ◽  
Marta Dziedzicka-Wasylewska
Keyword(s):  
Genetic Variants ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Dopamine D2

D1 and D2 dopaminergic systems in the rat basolateral amygdala are involved in anxiogenic-like effects induced by histamine

2011 ◽  
Vol 26 (4) ◽  
pp. 564-574 ◽  
Author(s):  
Maryam Bananej ◽  
Ahmad Karimi-Sori ◽  
Mohammad Reza Zarrindast ◽  
Shamseddin Ahmadi
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Basolateral Amygdala ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Dopamine D2 ◽  
D1 And D2 Receptors ◽  
Male Wistar Rats

Involvement of the dopamine receptors in the basolateral amygdala (BLA) in the effects of histamine on anxiety-like behaviors of the elevated plus maze in male Wistar rats was investigated. The results showed that bilateral intra-BLA injections of histamine (2.5, 5 and 7.5 µg/rat) induced an anxiogenic-like effect, revealed by decreases in percentage of open arm time (%OAT) and open arm entries (%OAE). Intra-BLA administration of dopamine D1 receptor agonist, SKF38393 (0.25 µg/rat), and dopamine D2 receptor agonist, quinpirole (0.03 and 0.05 µg/rat), decreased %OAT but not %OAE. Conversely, intra-BLA administration of dopamine D1 receptor antagonist, SCH23390 (0.5 and 1 µg/rat), and dopamine D2 receptor antagonist, sulpiride (0.3 and 0.5 µg/rat), increased %OAT and %OAE, suggesting an anxiolytic-like effect for both drugs. Interestingly, co-administration of a silent dose of SCH23390 or sulpiride prevented anxiogenic-like effects of SKF38393 and quinpirole, respectively. Conjoint administration of a sub-effective dose of SKF38393 (0.125 µg/rat) or quinpirole (0.01 µg/rat) along with lower doses of histamine (1 and 2.5 µg/rat) induced anxiolytic-like effects. On the other hand, intra-BLA pretreatment with a silent dose of SCH23390 (0.25 µg/rat) or sulpiride (0.1 µg/rat) prevented the anxiogenic-like effect of higher doses of histamine (5 and 7.5 µg/rat). No significant change was observed in total closed arm entries, as an index for motor activity of the animals. It can be concluded that the dopamine D1 and D2 receptors in the BLA may be involved in the anxiogenic-like effects induced by histamine.

Evidence for the heterotetrameric structure of the adenosine A2A–dopamine D2 receptor complex

2016 ◽  
Vol 44 (2) ◽  
pp. 595-600 ◽  
Author(s):  
Verònica Casadó-Anguera ◽  
Jordi Bonaventura ◽  
Estefanía Moreno ◽  
Gemma Navarro ◽  
Antoni Cortés ◽  
...  
Keyword(s):  
Structural Model ◽  
Dopamine D2 Receptor ◽  
Ex Vivo ◽  
D2 Receptor ◽  
Drug Dosage ◽  
D1 Receptor ◽  
Structural Basis ◽  
Dopamine D2 ◽  
Allosteric Mechanisms ◽  
Adenosine A2a

Heteromers of G-protein-coupled receptors (GPCRs) have emerged as potential novel targets for drug development. Accumulating evidence indicates that GPCRs can form homodimers and heteromers, with homodimers being the predominant species and oligomeric receptors being formed as multiples of dimers. Recently, heterotetrameric structures have been proposed for dopamine D1 receptor (D1R)–dopamine D3 receptor (D3R) and adenosine A2A receptor (A2AR)–dopamine D2 receptor (D2R) heteromers. The structural model proposed for these complexes is a heteromer constituted by two receptor homodimers. The existence of GPCR homodimers and heteromers provides a structural basis for inter-protomer allosteric mechanisms that might account for a multiplicity of unique pharmacological properties. In this review, we focus on the A2AR–D2R heterotetramer as an example of an oligomeric structure that is key in the modulation of striatal neuronal function. We also review the interfaces involved in this and other recently reported heteromers of GPCRs. Furthermore, we discuss several published studies showing the ex vivo expression of A2AR–D2R heteromers. The ability of A2AR agonists to decrease the affinity of D2R agonists has been reported and, on the basis of this interaction, A2AR antagonists have been proposed as potential drugs for the treatment of Parkinson's disease. The heterotetrameric structure of the A2AR–D2R complex offers a novel model that can provide new clues about how to adjust the drug dosage to the expected levels of endogenous adenosine.

Association between dopamine D2 receptor (DRD2) genetic variants and alcohol dependence in Han Chinese in Taiwan

2014 ◽  
Vol 220 (3) ◽  
pp. 1174-1175
Author(s):  
Pei-Chen Tsai ◽  
Chaio-Chicy Chen ◽  
Chun-Hung Pan ◽  
Wen-Chi Jan ◽  
Po-Hsiu Kuo ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Genetic Variants ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Han Chinese ◽  
Dopamine D2

scholarly journals α4-containing GABAA receptors on dopamine D2 receptor-expressing neurons mediate instrumental responding for conditioned reinforcers, and its potentiation by cocaine

2016 ◽  
Author(s):  
Tom Macpherson ◽  
Claire I Dixon ◽  
Patricia H. Janak ◽  
Delia Belelli ◽  
Jeremy J. Lambert ◽  
...  
Keyword(s):  
Drugs Of Abuse ◽  
Dopamine D2 Receptor ◽  
Conditioned Reinforcer ◽  
D2 Receptor ◽  
D1 Receptor ◽  
Medium Spiny Neurons ◽  
Conditioned Reinforcers ◽  
Behavioural Responses ◽  
Dopamine D2 ◽  
Specific Deletion

Abstract:Extrasynaptic GABAA receptors (GABAARs) composed of α4, β and δ subunits mediate GABAergic tonic inhibition and are pertinent molecular targets in the modulation of behavioural responses to drugs of abuse, including ethanol and cocaine. These GABAARs are highly expressed within the nucleus accumbens (NAc) where they influence the excitability of the medium spiny neurons (MSNs). Here we explore their role in modulating behavioural responses to reward-conditioned cues and the behaviour-potentiating effects of cocaine. α4-subunit constitutive knockout mice (α4-/-) showed higher rates of instrumental responding for reward-paired stimuli in a test of conditioned reinforcement (CRf). A similar effect was seen following viral knockdown of GABAAR α4 subunits within the NAc. Local infusion of the δ-GABAAR-preferring agonist, THIP, into the NAc had no effect on responding when given alone, but reduced cocaine potentiation of responding for conditioned reinforcers in wildtype but not α4-/- mice. Finally, specific deletion of α4-subunits from dopamine D2-, but not D1-receptor-expressing neurons, mimicked the phenotype of the constitutive knockout, potentiating CRf responding and blocking intra-accumbal THIP attenuation of cocaine-potentiated CRf responding. These data demonstrate that α4-GABAAR mediated inhibition of dopamine D2 receptor-expressing neurons reduces instrumental-responding for a conditioned reinforcer, and its potentiation by cocaine, and emphasise the potential importance of GABAergic signalling within the NAc in mediating cocaine’s effects.

Dopamine D2 Receptor and N-Methyl-D-Aspartate Receptor 2B Subunit Genetic Variants and Intelligence

2002 ◽  
Vol 45 (3) ◽  
pp. 128-130 ◽  
Author(s):  
Shih-Jen Tsai ◽  
Younger W.-Y. Yu ◽  
Ching-Hua Lin ◽  
Tai-Jui Chen ◽  
Sheau-Ping Chen ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D2 ◽  
Aspartate Receptor
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