Rationale: Dopamine D4 receptor gene polymorphism has been repeatedly associated with attention deficit hyperactivity disorder (ADHD) and related personality traits. We recently reported that motor hyperactivity in an animal model of ADHD was dose-dependently reversed by CP-293,019, a D4 receptor-selective antagonist. However, behavioral effects of this agent may not be attributed exclusively to D4 receptor blockade, since it interacts with other sites including serotonin receptors.
Objectives: To test further the hypothesis that D4 receptor blockade can reduce motor hyperactivity, behavioral effects of three chemically and pharmacologically dissimilar D4 antagonists were compared to that of ketanserin, a serotonin 5-HT(2A/2C) antagonist.
Methods: Selective dopamine lesions were made in male rats at postnatal day (PD) 5 with intracisternal 6-hydroxydopamine (100 microg) after desipramine pretreatment (25 mg/kg, SC) to protect noradrenergic neurons. Effects of D4 receptor-selective antagonists and ketanserin on lesion-induced motor hyperactivity were examined during the periadolescent period (postnatal days 23-26) with an infrared photobeam activity system.
Results: The D4 antagonists L-745,870 and U-101,958 dose-dependently inhibited motor hyperactivity in rats with neonatal lesions, whereas S-18126 lacked this effect at doses up to 30 mg/kg. None of these drugs affected motor behavior in sham control rats. In contrast, ketanserin produced apparent sedative effects in both lesioned and intact control rats without normalizing hyperactivity.
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.
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http://dx.doi.org/10.1007/s00213-002-1018-1 | DOI Listing |
Exp Neurol
January 2025
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. Electronic address:
Depression is one of the most common non-motor symptoms in Parkinson's disease (PD) and the hyperactivity of the lateral habenula (LHb) may contribute to depression. The present study was performed to investigate the effects and mechanisms of group I metabotropic glutamate receptors (mGluRs) in the LHb on PD-related depressive-like behaviors. Unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) were used to establish the PD rat model.
View Article and Find Full Text PDFClin Neurophysiol
January 2025
Ghent University, Department of Rehabilitation Sciences, Corneel Heymanslaan 10 9000 Ghent, Belgium; Ghent University Hospital, Department of Otorhinolaryngology, Corneel Heymanslaan 10 9000 Ghent, Belgium.
Objective: The study aimed to explore the vestibular function in children with neurodevelopmental disorders (NDDs).
Methods: Twenty-eight participants with a NDD (6 girls, 22 boys; 6-13 years; 9;3 ± 2;4 years) were enrolled in this pilot study. Sixteen participants had a single NDD (Autism Spectrum Disorder: n = 7, Developmental Coordination Disorder: n = 3; Attention Deficit/Hyperactivity Disorder: n = 6), the remaining 12 had comorbid NDDs.
Neurosci Bull
January 2025
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.
Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder influenced by both genetic and environmental factors, remains poorly understood regarding how its polygenic risk score (PRS) impacts functional networks and symptomology. This study capitalized on data from 11,430 children in the Adolescent Brain Cognitive Development study to explore the interplay between PRS, brain function, and behavioral problems, along with their interactive effects. The results showed that children with a higher PRS exhibited more severe attention deficits and rule-breaking problems, and experienced sleep disturbances, particularly in initiating and maintaining sleep.
View Article and Find Full Text PDFBMC Psychol
January 2025
School of Social Sciences, University of Mannheim, L13, 17, Mannheim, Germany.
Individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) often have overlooked motor difficulties which can be at least partially attributed to co-occurring conditions such as Developmental Coordination Disorder (DCD). Understanding the influence of DCD and motor difficulties is important to detect in children for early support. Accordingly, the present study examined the prevalence of DCD diagnoses, cases of probable DCD, and related impairments among German-speaking parents of children with ADHD.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Zoology Department, Faculty of Science, Cairo University, Giza, Egypt.
Due to the continuous exposure to bisphenol-A (BPA), the current study was conducted to evaluate taurine's neuroprotective action against BPA's adverse effect on the brain. Rats were grouped into control, BPA-treated rats, and taurine + BPA-treated rats. At the end of the 35-day treatment period, the memory of the rats was evaluated using the novel object test and the Y-maze test.
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