Search Results (142)

Background: Butyrophenone neuroleptics are used in veterinary practice—haloperidol in the capture and translocation of wild ungulates, azaperone in swine—and antipsychotics prescribed to owners are a recognised cause of accidental toxicosis in dogs and cats. Organ-level toxicity data for this drug class are nonetheless almost absent in any species. Intravenous lipid emulsion (ILE) is an established antidote in small-animal emergency medicine for lipophilic intoxications, but the veterinary evidence base consists of case reports with clinical endpoints, and no controlled study has examined what ILE does to the tissues themselves. This study used an acute rodent overdose model to provide that organ-level assessment. Methods: Forty male Wistar albino rats were randomised to four groups of ten: control (saline 2 mL/kg oral gavage), HP (17.5 mg/kg oral gavage), HP + ILE (17.5 mg/kg HP plus 20% ILE 7.5 mL/kg intravenously at 0.5 h and 8 h, an empirical regimen) and ILE alone. Endpoints were assessed at 24 h. Seventeen histopathological parameters across seven organs were scored semi-quantitatively by a blinded pathologist (n = 10 per group), with independent re-scoring of a stratified random 30% subsample by a second blinded pathologist. Serum total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and routine biochemistry were measured in animals with adequate serum (n = 34 and n = 35). Comparisons used Kruskal–Wallis and Mann–Whitney U tests with Benjamini–Hochberg false discovery rate (FDR) control. Results: Haloperidol produced significant injury in the liver, kidney, brain and testis (all p < 0.001 vs. control) and mild histological cardiac changes (degeneration p = 0.014; congestion p = 0.034); lung and eye were unaffected. Serum urea was markedly elevated in HP (67.4 ± 13.2 vs. 46.5 ± 8.8 mg/dL; p = 0.001, d = 1.82) and HP + ILE (61.5 ± 8.7 mg/dL; p = 0.003), with unchanged creatinine, and correlated strongly with renal histopathology (renal inflammation vs. urea ρ = 0.74, p < 0.001). ILE significantly attenuated histopathological injury in 8 of the 12 haloperidol-associated parameters after FDR correction (renal congestion q = 0.032, r = 0.70; testicular Johnsen score q = 0.032, r = 0.66); the testicular score improved significantly relative to HP (q = 0.032) but remained statistically indistinguishable from control (p = 0.072), which does not establish equivalence. ILE did not reduce serum urea (HP + ILE vs. HP, p = 0.26) and did not modify the mild histological cardiac changes (p ≥ 0.40); no functional or electrophysiological cardiac endpoint was assessed. No group difference was detected in serum TOS or OSI (p = 0.43 and p = 0.51), whereas TAS was significantly reduced in the ILE-alone group (p = 0.011); the biological interpretation of this TAS finding remains uncertain, because interference of residual lipaemia with the spectrophotometric assay could not be excluded and would also propagate to the derived OSI. No tissue oxidative marker was measured. Transaminases were not elevated by haloperidol and showed no correlation with hepatic histopathology (|ρ| ≤ 0.17, all p > 0.34). ILE alone caused no histopathological abnormality at this dose and time point. Inter-observer agreement was high (95.6% exact agreement; median weighted κ = 0.893). Conclusions: In this acute overdose model, ILE is associated with a differential and structurally incomplete histopathological response: microscopic injury improves in four organs while renal function does not, and the mild histological cardiac changes are unaltered. Serum transaminases did not reflect concurrent organ-level injury at 24 h. Serum TOS and OSI showed no detectable group differences, while TAS was reduced in the ILE-alone group with an uncertain biological interpretation. Given the analytical uncertainty and the limited sample size, these indices provided no usable surrogate information about organ-level injury in this model. These findings define which organ systems respond and require confirmation in target veterinary species before informing clinical practice. Full article

A naive Bayesian classifier (NBC) combined with principal component analysis (PCA) effectively differentiates the dose-dependent effects of certain groups of psychoactive drugs based on their impact on the amplitude–spectral characteristics of electrocorticograms (ECoG) in rats. This approach has been shown to be useful for pharmacological screening of agents with unknown or poorly understood activity. Despite previously obtained optimistic results, classification determination for some drugs was inaccurate, necessitating the search for possible ways to improve the predictive effectiveness of the proposed algorithm. One possible approach would be to use as input quantitative data not only the impact of the psychoactive drugs studied on the amplitude–spectral characteristics of ECoG but also connectivity changes, including the average coherence power of different pairs of leads. The aim of this study was to compare the accuracy of NBC in classifying the pharmacological mechanism of action of agents with well-known mechanisms (test set) using pharmaco-EEG data on changes in the amplitude–spectral characteristics of ECoG, coherence, and the combined use of two data sets. Materials and methods. Experiments were performed on Wistar rats with chronically implanted ECoG electrodes. The training set, relative to which the effects of the pharmacological agents from the test set were classified, were the matrices of effects of 12 pharmacological agents: the NMDA antagonist dizocilpine, the D2/D3 antagonists haloperidol and sulpiride, the M-anticholinergic tropicamide, the H1/5HT2A receptor blocker hydroxyzine, the acetylcholinesterase inhibitor galantamine, the alpha-2 adrenergic agonist dexmedetomidine, the alpha-2 adrenergic antagonist atipamezole, the adenosine receptor blocker caffeine and the GABA-mimetics aminophenylbutyric acid (phenibut), bromdihydrochlorophenylbenzodiazepine (phenazepam) and 5-ethyl-5-phenyl-2,4,6(1H,3H,5H)-pyrimidinetrione. The test set included various drugs with tropism for the targets of the training set drugs: dopamine receptor antagonists chlorpromazine, droperidol, tiapride and raclopride, H1-histamine blockers diphenhydramine and promethazine, 5-HT2-receptor blockers ritanserin and glemenserin, acetylcholinesterase inhibitor ipidacrine, alpha2-adrenergic receptor antagonist yohimbine, alpha2-adrenergic agonists medetomidine and xylazine, GABA-mimetics 5-ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione and chloral hydrate. The analysis of the ECoG signal included the calculation of 132 amplitude–spectral characteristics and 75 coherence indicators, which, using the PCA, led to new integrative indicators used for further classification of the NBC. Results and discussion. For each drug in the test set, the median similarity probability with a particular group from the training set was calculated, which was used to assess the classification quality. It was found that, when using the amplitude–spectral characteristics of ECoG, the proposed methodological approach allows for the identification of the ECoG effects of several groups of psychoactive drugs, including D2/D3-dopamine, M-cholinergic, H1-histamine, and 5-HT2-serotonin receptor blockers, AChE inhibitors, GABA-mimetics, and alpha-2-adrenergic receptor agonists and antagonists. This approach enabled the correct classification of 18 of 24 groups in the test set. When using changes in coherence indices as the initial data, the classification accuracy also amounted to 18 of 24 groups. When combining the two data sets, the number of correctly identified NBC groups was 20 of 24 groups. When comparing the classification during training (confusion matrix), it was found that coherence data or adding coherence data to the data based on changes in amplitude–spectral characteristics leads to a statistically significant (p < 0.01 in both cases) increase in accuracy. Conclusions. The obtained data demonstrated high accuracy in classifying the pharmacological activity of the test sample drugs using any of the three compared approaches. Despite the lack of statistically significant differences between them, classification based on the combined dataset demonstrated a higher number of “correct” similarities. This allows us to recommend the approach based on combined data of drug effects on amplitude–spectral characteristics and coherence as the most promising for further studies using pharmaco-EEG screening. Full article

The dopamine D₂ receptor (D2R) is one of the principal therapeutic targets for the treatment of schizophrenia and other neuropsychiatric disorders. Understanding how ligands with different pharmacological profiles interact with D2R is essential for the rational design of safer and more effective antipsychotic drugs. In this work, Molecular Dynamics (MD) simulations combined with Quantum Theory of Atoms in Molecules (QTAIM) analysis were employed to investigate the electronic nature of protein–ligand interactions in D2R embedded in a neuronal membrane environment. Representative agonists (dopamine and rotigotine) and antipsychotics from different generations (haloperidol, risperidone, and aripiprazole) were analyzed to identify interaction patterns associated with distinct pharmacological activities. The agonist-bound simulations revealed recurrent interactions involving the serine-rich region, whereas the antipsychotic-bound systems exhibited more persistent contacts within the central aromatic region of the binding pocket. These observations suggest ligand-associated interaction tendencies rather than universal determinants of agonism or antagonism. Furthermore, aripiprazole displayed a unique interaction profile characterized by enhanced coupling with the PIF connector, suggesting a distinct modulation of the TM6 toggle switch compared with other antipsychotics. The integration of MD and electron density topology revealed ligand-specific interaction networks associated with distinct pharmacological profiles at D2R. The interaction patterns identified in this study highlight characteristic interaction motifs associated with ligand-specific pharmacological profiles and provide mechanistic insights that may support the rational design of novel dopaminergic therapeutics. Full article

Background/Objectives: Migraine is markedly more prevalent among individuals with bipolar disorder (BD) than in the general population. The two disorders share overlapping pathophysiological mechanisms, including neuroinflammation, oxidative stress, and genetic vulnerability. However, the potential bidirectional efficacy of pharmacological agents approved for one condition on the other remains unclear. This study aimed to evaluate cross-disorder pharmacological efficacy between migraine and bipolar disorder. Methods: We systematically searched Medline and the Cochrane Central Register of Controlled Trials (PROSPERO registration: CRD420251130780) for randomized controlled trials (RCTs) assessing (1) concurrent treatment effects in comorbid BD–migraine samples, (2) efficacy of migraine treatments in BD, or (3) efficacy of BD treatments in migraine. Searches included guideline-recommended drugs for either disorder, without language or date restrictions. Results: A total of 32 RCTs met the inclusion criteria. Fifteen studies evaluated migraine drugs in BD, and sixteen evaluated BD drugs in migraine. No RCTs were identified that simultaneously assessed both conditions within the same sample. Valproate was the only agent demonstrating consistent, replicated efficacy in both conditions, supporting true cross-disorder benefit. Haloperidol and chlorpromazine showed limited evidence for acute anti-migraine efficacy, based solely on placebo-controlled studies, whereas all other guideline-recommended BD drugs lacked evidence of benefit for migraine. Conversely, topiramate, while effective for migraine, was inferior to valproate in BD outcomes, and lamotrigine was effective for BD only when compared with placebo. Conclusions: Valproate remains the sole pharmacological agent with robust evidence of bidirectional efficacy in migraine and BD. Most other guideline-recommended medications show disorder-specific effects, highlighting the need for integrative trials addressing pharmacological overlap in comorbid migraine–BD samples. Full article

Tardive dyskinesia (TD) is a persistent hyperkinetic movement disorder associated with prolonged dopamine D2 receptor blockade, particularly during chronic haloperidol (HP) exposure. Emerging evidence suggests that TD-like pathology is sustained by an interconnected redox–mitochondrial–inflammatory network within striatal circuits; however, the regulatory architecture of this network remains incompletely defined. Hyperoside (HS), a flavonol glycoside with cytoprotective properties, has been implicated in cellular stress-response modulation, yet its role in antipsychotic-induced motor dysfunction remains unclear. In this study, a six-group mechanistic design was employed in which rats received HP (1 mg/kg, i.p., 21 days) to induce TD-like orofacial dyskinesia (OD), quantified by vacuous chewing movements (VCMs) and tongue protrusions (TPs). HS (30 mg/kg, i.p.) was administered alone or in combination with HP, with or without pharmacological inhibition of nuclear factor erythroid 2–related factor 2 (Nrf2) using ML385. HP exposure induced progressive dyskinetic behavior accompanied by oxidative and nitrosative stress, mitochondrial dysfunction, increased pro-inflammatory cytokines, and elevated caspase-3 activity in the striatum. HS significantly attenuated behavioral abnormalities while restoring redox balance, preserving mitochondrial enzyme activities, and reducing inflammatory and apoptotic signaling. Notably, Nrf2 inhibition intensified molecular pathology without proportionally worsening behavioral outcomes, indicating a dissociation between biochemical vulnerability and overt motor expression. Furthermore, ML385 markedly attenuated HS-mediated protection across multiple endpoints. Collectively, these findings support a potential protective role for Nrf2-related regulatory mechanisms in limiting network destabilization in TD-like pathology, while highlighting the importance of integrated stress-response pathways in modulating disease progression. Full article

Background/Objectives: As the prevalence of depression and the use of antidepressants have risen steadily in the last decade, new treatment options are needed. Aloysia gratissima var. gratissima ethanol extract has previously shown antidepressant-like activity, and the present study was conducted to identify the active fraction and clarify the possible mechanisms of action. Methods: Tail suspension (TST) and forced swimming (FST) behavioral tests were performed, and possible mechanisms of action were elucidated using serotonergic, dopaminergic, adrenergic, and GABAergic system antagonists. UPLC-DAD-MS analyses were performed to identify compounds in active fractions, and molecular docking studies were carried out to determine the binding affinities of these compounds to serotonergic and dopaminergic receptors (5-HT_1A, 5-HT_2A, 5-HT₃, and D₂R). Results: Ethyl acetate and butanol fractions were found to decrease immobility time in FST. The reduction in immobility time during the FST caused by the ethyl acetate fraction was reversed by pretreating mice with WAY100635 (5-HT_1A antagonist), ketanserin (a 5-HT_2A antagonist, ondansetron (5-HT₃ antagonist), or haloperidol (D₂ antagonist). UPLC-DAD-MS analysis revealed a similar composition for the ethyl acetate and butanol fractions of A. gratissima var. gratissima. Pharmacokinetic predictions suggest that only a few of the identified compounds have the potential to permeate the blood–brain barrier, and molecular docking simulations showed that compounds such as 13-oxooctadecadienoic acid, ferulic acid, and coumaric acid have binding affinities to the druggable site of serotonergic and dopaminergic receptors. Conclusions: These results suggest that the Agg ethyl acetate fraction possesses antidepressant-like activities, altering dopaminergic and serotonergic system functions. Computational simulations also suggest that some of the identified compounds have binding affinities to the 5-HT_1A, 5-HT_2A, 5-HT₃, and D₂R receptors. Full article

Parkinson’s disease (PD) has been associated with some types of food and drugs. Here, we query PubMed for the association of PD with foods and drugs, using a list of 217,776 compounds derived from the Human Metabolome Database (HMDB). To calculate associations, a Python script was developed to query PubMed for co-citations of PD with each compound, and adjust this count for compound abundance. Notably, PD is found to be associated with small-molecule drugs, adjunctive therapies, contraindicated drugs, diagnostic agents, biomarkers, conditional essential molecules, and inducers. Drugs include L-dopa (49%), carbidopa (63%), benserazide (50%), entacapone (74%), tolcapone (56%), rasagiline (76%), selegiline (46%), pargyline (4%), ropinirole (61%), pramipexole (56%), lisuride (27%), cabergoline (16%), bromocriptine (12%), and zonisamide (9%). Adjunctive therapies include droxidopa (33%), trihexyphenidyl (28%), biperiden (17%), amantadine (24%), memantine (7%), rivastigmine (13%), donepezil (6%), galantamine (4%), domperidone (6%), clonazepam (4%), tetrabenazine (16%), mazindol (13%), quetiapine (6%), and clozapine (4%). Contraindicated drugs include haloperidol (4%), sulpiride (3%), and methyldopa (6%). Diagnostic agents include FP-CIT (60%) and beta-CIT (43%). Biomarkers include 3-methoxytyrosine (48%) and homovanillic acid (12%). Endogenous cofactors include tetrahydrobiopterin (4%) and Coenzyme Q10 (4%). Chemical inducers of PD include 6-hydroxydopamine (40%), N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 78%), tetrahydropyridine (77%), probenecid (4%), quinolinic acid (4%), 1,2,3,4-tetrahydroisoquinoline (TIQ, 16%), salsolinol (32%), rotenone (25%), and β-Methylamino-L-alanine (BMAA, 29%). Notably, our study highlights conditional essential endogenous cofactors associated with PD and emphasizes rational directions for investigation in PD. Full article

This study evaluated long-term trends in the prevalence of use of atypical and typical antipsychotic drugs (APDs), both as classes of drugs and as individual drugs, among adult inpatients in the United States (US). The Health Facts^® database developed by Cerner Corporation was used to analyze the prevalence of APD use among adult inpatients aged 18 years or older who were administered at least one antipsychotic medication order during hospitalization between 1 January 2000 and 31 December 2016. The prevalence of APD use was standardized by age, sex, race, and census region. Typical and atypical antipsychotic treatment patterns in the US differed over this period. While the use of atypical APDs increased overall, the use of typical antipsychotic medications decreased, but remained more prevalent. Overall, haloperidol and prochlorperazine were the two most administered antipsychotic medications throughout the study period. From 2000 to 2011, prochlorperazine and haloperidol were the first- and second-most prescribed typical APDs, respectively; haloperidol became the most administered antipsychotic of this class as of 2012. Quetiapine was the most administered atypical antipsychotic medication, followed by risperidone and olanzapine until 2014, after which olanzapine was the second-most administered atypical APD. There was a notable decline in the use of atypical antipsychotics medications between 2005 and 2008, which may reflect the impact of the Food and Drug Administration’s warnings and the American Diabetes Association’s consensus position, but only for a short time. The usage patterns observed in this study support existing evidence of substantial off-label use of antipsychotic drugs in the US. Full article

Objective: To scope the available literature on antipsychotic treatment in substance-induced psychotic disorders, summarize evidence across substance categories, and highlight priorities for future research. Methods: This scoping review followed Arksey and O’Malley’s framework and PRISMA-ScR guidelines. A systematic search of PubMed, Scopus, Embase, PsycINFO, and Cochrane Library (January 1985–August 2025) identified studies examining antipsychotic treatment in cannabis-, stimulant-, and hallucinogen-induced psychoses. Two reviewers independently screened studies and extracted data using a standardized form. Given marked heterogeneity, findings were synthesized descriptively. Results: Seventeen studies met inclusion criteria: 3 randomized controlled trials (17.6%), 10 observational studies (58.8%), and 4 case series (23.5%). Most evidence involved cannabis-induced (n = 7) and methamphetamine-induced (n = 6) psychosis. Randomized trials showed comparable efficacy between risperidone and haloperidol for cannabis-induced psychosis, and between quetiapine and haloperidol for methamphetamine-induced psychosis. Case series suggested potential benefits of third-generation antipsychotics such as lurasidone and cariprazine. No controlled studies were identified for cocaine- or hallucinogen-induced psychoses. Conclusions: Evidence for antipsychotic treatment in substance-induced psychoses remains scarce and uneven. While conventional antipsychotics appear effective for cannabis- and methamphetamine-related presentations, other substances remain virtually unstudied. Substantial evidence gaps and limited methodological quality highlight urgent research needs. Full article

Single-cell RNA-sequencing has transformed our understanding of alveolar epithelial type 2 (AT2) cells and alveolar lipofibroblasts (LIFs) during lung injury and repair. Both cell types undergo dynamic transitions through intermediate states that determine whether the lung proceeds toward regeneration or fibrosis. Emerging evidence highlights reciprocal paracrine signaling between AT2/AT1 transitional cells and LIF-derived myofibroblasts (aMYFs) as a key regulatory axis. Among these, amphiregulin (AREG)–EGFR signaling functions as a central profibrotic pathway whose inhibition can restore alveolar differentiation and repair. The human WI-38 fibroblast model provides a practical platform to study the reversible LIF–MYF switch and screen antifibrotic and pro-regenerative compounds. Candidate therapeutics including metformin, haloperidol and FGF10 show promise in reprogramming fibroblast and epithelial states through metabolic and signaling modulation. Integrating WI-38-based assays, alveolosphere co-cultures, and multi-omics profiling offers a translational framework for identifying interventions that halt fibrosis and actively induce lung regeneration. This review highlights a unifying framework in which epithelial and mesenchymal plasticity converge to define repair outcomes and identifies actionable targets for promoting alveolar regeneration in chronic lung disease. Full article

Background: Adolescence is a vulnerable period for the onset of severe psychiatric conditions, such as psychotic spectrum disorders. Non-adherence to antipsychotics is a common problem in young people with these conditions and paves the way for relapse, rehospitalization, and functional impairment. Co-occurring substance use disorders (SUDs) further undermine adherence and worsen outcomes. Long-acting injectable antipsychotics (LAIs) improve adherence and outcomes in adults, but none are licensed for use in individuals under 18. This review seeks to distill the available evidence on LAIs’ use in adolescents, from efficacy to safety, and to outline clinical practice recommendations. Methods: A narrative review was conducted. The evidence was organized by drug class: risperidone, paliperidone, aripiprazole, and other antipsychotics (olanzapine, haloperidol, first-generation depots). Results: Evidence in adolescents remains sparse and heterogeneous. Risperidone LAI has shown improvements in symptom severity, functioning, and behavioral control in bipolar disorder and schizophrenia, though commonly associated with side effects. Paliperidone palmitate demonstrated benefit in first-episode schizophrenia and autism spectrum disorder with intellectual disability, reducing hospital use but carrying risks of EPS and hyperprolactinemia. Aripiprazole LAI showed functional gains, short-term tolerability, and encouraging acceptance in case reports. Other LAIs were used in highly resistant cases with some clinical benefit, though extrapyramidal adverse events were common. Conclusions: The current literature provides limited data, and no clinical guidelines exist for the use of LAI in adolescents. Nonetheless, off-label use is reported in selected cases in clinical practice. Best practice is to start with oral stabilization, then use the lowest effective LAI with psychosocial support and close monitoring. When SUD co-occurs, LAIs may also help mitigate risks related to misuse/diversion of oral medication, provided that care includes systematic SUD screening and early intervention. Prospective controlled studies are urgently needed to establish long-term efficacy and safety in this vulnerable population. Full article

Background: Schizophrenia (SCZ) is a psychiatric disorder that negatively impacts patients’ quality of life, frequently inducing difficulties in managing day-to-day tasks. Current research is persistently working on finding therapeutic methods to alleviate the positive and negative symptoms, as well as the associated cognitive dysfunctions. Since the main therapeutic approach in SCZ is antipsychotics, the current study aimed to explore the effects of typical (haloperidol, HAL) vs. atypical (risperidone, RIS) antipsychotics on the cognitive functions in an animal model (Danio rerio) of SCZ, obtained by ketamine (KET) administration. Methods: The cognitive evaluation of the zebrafish was performed using memory and learning tests based on two stimuli: food and colours (i.e., T memory test and novel object recognition (NOR) test, respectively). Results: According to the behavioural analyses, HAL significantly enhanced the cognitive performances of the SCZ model, as compared to RIS. Nonetheless, HAL and RIS exhibited comparable effects on social behaviour in the SCZ model. Interestingly, both HAL and RIS enhanced the interest for the novel object in the NOR test in control individuals, but significantly decreased it in the SCZ model. The interaction between KET and RIS could exhibit sedative properties. Conclusions: Both typical (HAL) and atypical (RIS) antipsychotics alleviated cognitive, socio-affective, and decision-making impairments in a ketamine-based adult zebrafish model of schizophrenia. HAL was more effective, particularly in food-stimulated decision-making compared to novel object or social stimuli. Colour influenced behavioural responses, with silver linked to prey/feeding effects and red perceived as aversive. The KET–RIS combination induced exploratory impairments, possibly due to sedative effects. These findings highlight differential pharmacological and ethological modulation of schizophrenia-like behaviours. Full article

Background: It has recently been proposed that the retina plays an important modulatory role in the control of motor function that is usually attributed exclusively to the function of the nigro-striatal dopamine (NSD) system. Indeed, it has been proposed further that Parkinson’s disease (PD) begins in and progresses from the retina and may be effectively treated from there. While previous intraocular work has employed intravitreal (IVIT) administration of toxins to induce experimental PD, the first study series reported here examines the effect of IVIT haloperidol on motor performance while the second study examines the effect of IVIT haloperidol on the unilateral rotation model of PD, both in a circadian context. Methods: Motor tests included open field performance and the latency to perform three motor tests after the IVIT injection of haloperidol with and without amphetamine pretreatment. In a second study, IVIT injections of the melatonin antagonist ML-23 or L-dopa were made after unilateral lesions of the NSD in rats that were placed in a rotometer examining spontaneous ipsilateral and contralateral turning. Results: IVIT haloperidol produced robust changes in several motor parameters during the light and dark phase of the LD cycle which were enhanced by amphetamine pretreatment. In the second study, while IVIT L-dopa had only a minor effect on spontaneous rotation during the light phase, IVIT haloperidol produced a robust effect upon ipsilateral turning. The reduction in spontaneous ipsilateral turning was seen after IVIT injections into the eye ipsilateral or contralateral to the hemisphere in which NSD destruction occurred. Reduced turning was seen during both the light and dark phases of the L/D cycle. Conclusions: These results illustrate that IVIT injections of DA and melatonin receptor antagonists can differentially alter motor function via the retina. This suggests that the retina may be a treatment target not only for PD but also for other DA- and melatonin-mediated disorders such as drug addiction, psychosis and schizophrenia. Full article

The antipsychotic drug haloperidol is found on the WHO list of essential drugs. In vitro, haloperidol demonstrates binding affinity for various receptors, including histamine H₂ receptors (H₂Rs). Several cardiac effects of haloperidol are known, but it remains unclear whether H₂Rs are involved. Here, the hypothesis was tested that haloperidol has the potential to act as either an agonist or an antagonist of human cardiac H₂Rs. The contractile effects of haloperidol were studied in isolated left and right atrial preparations from transgenic mice overexpressing human H₂Rs in the heart (H₂-TG), and compared to human atrial preparations from adult patients. Haloperidol reduced the histamine-stimulated force of contraction in the human atrial preparations as well as the histamine-stimulated force of contraction and beating rate in the left and right atrial preparations from the H₂-TG, respectively. Moreover, haloperidol reduced the isoprenaline-stimulated force of contraction in the human atrial preparations. In the wild-type mouse preparations, haloperidol only reduced the isoprenaline-stimulated beating rate in the right atria, but not the force in the left atria. Principally, haloperidol is capable of acting as an antagonist of both H₂Rs and β-adrenoceptors in the human heart. However, the effects are only relevant at very high doses of haloperidol, which are never or seldom achieved in practice. Full article

The main objective of this study was to assess whether donepezil or haloperidol, after a 10-day training period, could inhibit inhibitory avoidance and alter learned behavior. To assess memory impairment, zebrafish were trained in a light/dark tank over a 20-day period: 10 days without mechanical stimulation and 10 days with mechanical stimulation. Three behavioral parameters were recorded, i.e., latency to enter the dark compartment, time spent in the dark zone, and the number of entries into the dark area. Following the training phase, scopolamine was administered to induce amnesia. Donepezil and haloperidol were used as reference compounds for comparison. Subsequently, zebrafish were placed in a cylindrical tank, and spontaneous exploratory behavior was evaluated by measuring the amount of time spent in the upper region of the tank, an indicator of anxiety-related behavior. The behavioral data from the training phase were used to establish a baseline profile of zebrafish performance in the light/dark tank. Scopolamine administration significantly altered all of the measured behavioral parameters, including exploratory behavior in the cylindrical tank. Notably, donepezil or haloperidol prevented the memory-impairing effects of scopolamine, supporting the use of the light/dark tank paradigm to evaluate the efficacy of pharmacological agents in reversing scopolamine-induced amnesia in zebrafish. Full article