Disease relevance of Drd4

• CONCLUSIONS: Motor hyperactivity in this ADHD model was selectively antagonized by three of four dopamine D4 receptor antagonists evaluated, encouraging clinical assessment of D4 antagonists in patients with ADHD [1].

Psychiatry related information on Drd4

• RATIONALE: Dopamine D4 receptor gene polymorphism has been repeatedly associated with attention deficit hyperactivity disorder (ADHD) and related personality traits [1].
• Effects of selective dopamine D4 receptor antagonist, L-741,741, on sleep and wakefulness in the rat [2].
• The novel dopamine D4 receptor agonist (PD 168,077 maleate): doses with different effects on locomotor activity are without effect in classical conditioning [3].
• These present studies evaluated the potential cognitive enhancing properties of A-412997 in rat models of ADHD (5-trial repeated acquisition inhibitory avoidance in Spontaneous Hypertensive Rat pups) and short-term memory (Social Recognition), in comparison with the less selective dopamine D4 receptor agonists PD168077 and CP226269 [4].

High impact information on Drd4

• The dopamine D4 receptor in prefrontal cortex (PFC) plays a key role in normal mental functions and neuropsychiatric disorders [5].
• They are an ionotropic glutamate receptor subunit NMDA-2C, two GABA(A) receptor subunits, i.e., GABA(A)-epsilon and GABA(A)-theta, and a dopamine receptor D4 [6].
• In the present study amperozide displayed low affinity for several serotonin receptor subtypes as well as for the dopamine D4 receptor transfected in COS7 cells (Ki D4.2 = 769 nmol/L and Ki D4.4 = 384 nmol/L) [7].
• Based on DNA macoarray analyses, DCHP down-regulated the levels of gene expression of the dopamine D4 receptor at 4 weeks old in both the midbrain and the striatum, and the dopamine transporter in the midbrain at 8 weeks old 1.7- to 2-fold [8].
• Furthermore, bisphenol A decreased by more than twofold gene expression levels of the dopamine D4 receptor at 4 weeks of age and the dopamine transporter at 8 weeks of age [9].

Chemical compound and disease context of Drd4

• Effects of dopamine D4 receptor-selective antagonists on motor hyperactivity in rats with neonatal 6-hydroxydopamine lesions [1].

Biological context of Drd4

• Comparison of the binding kinetics of [(125)I] L-750667 and [(3)H] spiperone revealed B(max) values of 134+/-27 fmol/mg and 219+/-47 fmol/mg respectively, indicating that the dopamine D4 receptor is a major component of D2-like dopamine receptors in the rat retina [10].
• Dopamine D4 receptor density was, because of the absence of a dopamine D4 receptor specific [3H]ligand, determined by the difference between the number of binding sites for [3H]nemonapride and [3H]raclopride [11].
• PD-168077, a selective dopamine D4 receptor agonist, induces penile erection when injected into the paraventricular nucleus of male rats [12].
• Endogenous levels of dopamine D4 receptor mRNA in rat striatum are very low and, therefore, reverse transcription and subsequent amplification were used for quantification [11].
• Tissue distribution of radioiodinated FAUC113: assessment of a pyrazolo(1,5-a) pyridine based dopamine D4 receptor radioligand candidate [13].

Anatomical context of Drd4

• Dopamine D4 receptor-mediated presynaptic inhibition of GABAergic transmission in the rat supraoptic nucleus [14].
• A subpopulation of neurons in the medial prefrontal cortex encodes emotional learning with burst and frequency codes through a dopamine D4 receptor-dependent basolateral amygdala input [15].
• A strong dopamine D4 receptor protein immunoreactivity displaying the same localization of dopamine D2 receptor protein was observed in pial and mesenteric arteries, but not in renal artery branches [16].
• In renal tubules, the epithelium of collecting tubules showed the highest dopamine D4 receptor protein immunoreactivity, followed by the epithelium of proximal and distal tubules [17].
• No dopamine D4 receptor protein immunoreactivity was observed in the epithelium of the loop of Henle [17].

Associations of Drd4 with chemical compounds

• Two benzamide derivatives as dopamine D4 receptor antagonists, YM-50001(4) and N- [2-[4-(4-chlorophenyl]piperizin-1-yl]ethyl]-3-methoxybenzamide (9), were labeled by positron-emitter (11C), and their pharmacological specificities to dopamine D4 receptors were examined by quantitative autoradiography and positron emission tomography (PET) [18].
• Both the dopamine D3 receptor antagonist GR103691 (1 mg/kg) and the dopamine D4 receptor antagonist L745870 (1 mg/kg) partially antagonized the discriminative stimulus effects of cocaine (10 mg/kg) and the cocaine (10 mg/kg)-like discriminative stimulus effects of R(+)-7-OH-DPAT (0.3 mg/kg) [19].
• L-745,870 (3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1-1H-pyrollo[2,3-b] pyridine), a selective dopamine D4 receptor antagonist, reverted the quinpirole inhibition with greater potency (IC50=8.7 nM) than that of the dopamine D2/D3 receptor antagonist sulpiride and raclopride (IC50=4804 and 788 nM, respectively) [20].
• We here describe the effect of a one-month treatment with haloperidol on dopamine D4 receptor mRNA and protein levels in rat striatum [11].
• The dopamine D4 receptor antagonist L-745,870: effects in rats discriminating cocaine from saline [21].

Analytical, diagnostic and therapeutic context of Drd4

• Renal denervation abolished perivascular dopamine D4 receptor protein immunoreactivity [17].
• Autoradiography indicated partial displacement of [3H]PNU-101958 by unlabeled dopamine D4 receptor ligands without regional selectivity, and lack of selective labeling with [125I]RBI-257 [22].
• The postnatal development of rat brain dopamine D4 receptor gene expression was studied in animals 1 day to 1 year old, using the polymerase chain reaction technique [23].

References