Dopamine Receptor Research Articles

Discovery of NLX-266, an Orally Available and Metabolically Stable ERK1/2-Biased 5-HT1AR Agonist with Superior Antidepressant and Antiparkinsonian Activity.

We report the discovery of NLX-266 (31), an orally available and metabolically stable ERK1/2-biased 5-HT1A receptor agonist, which demonstrates both enhanced antidepressant and antiparkinsonian-like activities. A new series of 1-(1-benzoylpiperidin-4-yl)methanamine derivatives were synthesized and screened for their affinity and selectivity toward the 5-HT1A receptor. Notably, 31 exhibited exceptional binding affinity (pKi > 10) and selectivity (>1000×) over the adrenergic α1 and dopaminergic D2 receptors. In vitro functional assays revealed that 31 preferentially activates ERK1/2 phosphorylation, correlating with significant antidepressant effects in the forced swim test in rats at low doses (MED = 0.63 mg/kg p.o.). Furthermore, 31 demonstrated potent antiparkinsonian effects by reversing haloperidol-induced catalepsy at very low doses (MED = 0.04 mg/kg p.o.). The pharmacokinetic profile of 31 indicates favorable exposure and a prolonged half-life following oral administration. These findings suggest that 31 is a promising candidate for future exploration aiming at treatment of depression and/or Parkinson's disease.

Unique and overlapping mechanisms of valbenazine, deutetrabenazine, and vitamin E for tardive dyskinesia

In 2017, the Food and Drug Administration (FDA) approved valbenazine and deutetrabenazine, two vesicular monoamine transporter 2 (VMAT2) inhibitors, as treatments for tardive dyskinesia (TD). Additionally, some trials have suggested that vitamin E may benefit TD patients. However, the mechanistic basis for these treatments remains unclear. The objective of this study was to analyze and compare the mechanisms of valbenazine, deutetrabenazine, and vitamin E in TD treatment utilizing network pharmacology and molecular docking approaches. Putative target genes associated with valbenazine, deutetrabenazine, and vitamin E were retrieved from the PharmMapper, CTD, GeneCards, SwissTargetPrediction, and DrugBank databases. TD-related targets were identified using the GeneCards, DisGeNET, OMIM, and TTD databases. A protein-protein interaction (PPI) network was created to identify core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via DAVID, and Cytoscape was used to build a drug-pathway-target-disease network. Molecular docking evaluated drug-target interactions. A total of 32, 36, and 62 targets relevant to the treatment of TD were identified for valbenazine, deutetrabenazine, and vitamin E, respectively. PPI and KEGG pathway analyses suggested that valbenazine and deutetrabenazine may influence TD through the dopaminergic synapse signaling pathway via common core targets (e.g., Dopamine Receptor D1 (DRD1), DRD2, Monoamine Oxidase B (MAOB), Solute Carrier Family 6 Member 3 (SLC6A3), SLC18A2) and specific targets (DRD3 for valbenazine, MAOA for deutetrabenazine). Vitamin E may affect TD by targeting the PI3K-Akt pathway through AKT Serine/Threonine Kinase 1 (AKT1), Brain-Derived Neurotrophic Factor (BDNF), Insulin (INS), Nitric Oxide Synthase 3 (NOS3), and Toll-Like Receptor 4 (TLR4). This study provides insights into the common and unique molecular mechanisms by which valbenazine, deutetrabenazine, and vitamin E may treat TD. Pharmacological experiments should be conducted to verify and further explore these results. The findings offer a theoretical basis for further pharmacological investigation and a resource for TD drug screening.

Tactile stimulation ameliorates haloperidol-induced movement disturbances in rats by promoting neuromodulation on dopaminergic and glutamatergic systems in nigrostriatal brain area.

Tactile stimulation ameliorates haloperidol-induced movement disturbances in rats by promoting neuromodulation on dopaminergic and glutamatergic systems in nigrostriatal brain area.

Repeated treatment with JWH-018 progressively increases motor activity and aggressiveness in male mice: involvement of CB1 cannabinoid and D1/D2 dopaminergic receptors.

Repeated treatment with JWH-018 progressively increases motor activity and aggressiveness in male mice: involvement of CB1 cannabinoid and D1/D2 dopaminergic receptors.

Exploration of bioactive compounds in Benincasa hispida seeds: Insight into their therapeutic potential for Alzheimer's disease management using computer-aided drug design platform.

Alzheimer's disease (AD) is primarily caused by abnormal protein accumulation, such as beta-amyloid plaques and tau tangles, leading to neuronal damage via oxidative stress, neuroinflammation, synaptic dysfunction, and progressive brain atrophy. It is crucial to address and explore alternative therapeutic candidates. Based on traditional reports, the present study investigates the phytochemicals present in Benincasa hispida (Thunb.) Cogn. seeds and their potency against AD. Primarily, four different solvent systems have been used for crude extraction, and simultaneously fifty-one phytochemicals (BH_P1 to BH_P51) have been selected through chromatography-mass spectrometry (GC-MS) for further study. Five putative AD-associated targets, acetylcholinesterase (AChE), butyryl cholinesterase (BChE), estrogen receptor alpha (ERα), serotonin transporter (SERT), and D2 dopamine receptor (DRD2), were used to explore the individual therapeutic efficacy in the form of docking score using the PyRx 0.8-AutoDock 4.2 platform. According to the docking score (kcal/mol.), BH_P19, BH_P20, BH_P30, BH_P18/BH_P31, and BH_P17 are promising ones. Further, the drug-likeness profiles and ligand stability with AChE for 100 nanoseconds in the molecular dynamics simulation study revealed that BH_P19 was the lead therapeutic candidate among all. Overall, the integration of spectral techniques and computational investigations together highlights and encourages the exploration of natural regimens for AD.

Dynamics of two distinct memory interactions during water seeking in Drosophila

Forming and forgetting memories shape our self-awareness and help us face future challenges. Therefore, understanding how memories are formed and how different memories interact in the brain is important. Previous studies have shown that thirsty flies sense humidity through ionotropic receptors, which help them locate water sources. Here, we showed that thirsty flies can be trained to associate specific odors with humidity to form a humidity memory that lasts for 30 min after association. Humidity memory formation requires the Ir93a and Ir40a ionotropic receptors, which are essential for environmental humidity sensing. Water memory takes precedence, leading to the forgetting of humidity memory by activating a small subset of dopaminergic neurons called protocerebral anterior medial (PAM)-γ4, that project to the restricted region of the mushroom body (MB) γ lobes. Adult-stage-specific silencing of Dop2R dopaminergic receptors in MB γ neurons prolongs humidity memory for 3 h. Live-brain calcium imaging and dopamine sensor studies revealed significantly increased PAM-γ4 neural activity after odor/humidity association, suggesting its role in forgetting the humidity memory. Our results suggest that overlapping neural circuits are responsible for the acquisition of water memory and forgetting humidity memory in thirsty flies.

Alterations in dopaminergic innervation and receptors in focal cortical dysplasia.

Focal cortical dysplasia (FCD) type 2 is the most common malformation of cortical development associated with pharmaco-resistant focal epilepsy and frequently located in the frontal cortex. Neuropathological hallmarks comprise abnormal cortical layering and enlarged, dysmorphic neuronal elements. Fundamentally altered local neuronal activity has been reported in human FCD type 2 epilepsy surgical biopsies. Of note, FCD type 2 emerges during brain development and forms complex connectivity architectures with surrounding neuronal networks. Local cortical microcircuits, particularly in frontal localization, are extensively modulated by monoaminergic axonal projections originating from the brainstem. Previous analysis of monoaminergic modulatory inputs in human FCD type 2 biopsies suggested altered density and distribution of these monoaminergic axons; however, a systematic investigation is still pending. Here, we perform a comprehensive analysis of dopaminergic (DA) innervation, in human FCD type 2 biopsies and in the medial prefrontal cortex (mPFC) of an FCD type 2 mouse model [mechanistic target of rapamyin (mTOR) hyperactivation model] during adolescent and adult stages. In addition, we analyse the expression of dopamine receptor transcripts via multiplex fluorescent RNA in situ hybridization in human specimens and the mPFC of this mouse model. In the mTOR hyperactivation mouse model, we observe a transient alteration of DA innervation density during adolescence and a trend towards decreased innervation in adulthood. In human FCD type 2 areas, the overall DA innervation density is decreased in adult patients compared with control areas from these patients. Moreover, the DA innervation shows an altered lamination pattern in the FCD type 2 area compared with the control area. Dopamine receptors 1 and 2 appear to be differentially expressed in the dysmorphic neurons in human samples and mTOR-mutant cells in mice compared with normally developed neurons. Intriguingly, our results suggest complex molecular and structural alterations putatively inducing impaired DA neurotransmission in FCD type 2. We hypothesize that this may have important implications for the development of these malformations and the manifestation of seizures.

The Prosperity and Adversity of M4 Muscarinic Acetylcholine Receptor Activators in the Treatment of Neuropsychiatric Disorders.

Since the serendipitous discovery of chlorpromazine in the 1950s, almost all current anti-schizophrenia drugs utilize the same mode of action by blocking the dopamine receptors in the brain. Unfortunately, these only treat part of the symptoms and are ineffective in almost 30% of patients. The recent FDA approval of Cobenfy, a coformulation of xanomeline, a M1/M4 muscarinic acetylcholine receptor (mAChR) agonist, and a peripherally restricted pan-mAChR blocker, has propelled the M4R as a validated and novel antipsychotic target. With >25 years of history in developing xanomeline, significant challenges remain in developing M4R activators, either at the ACh orthosteric binding site or allosterically via secondary less-conserved binding sites. Herein, we summarize recent successes and failures of M4R agonists and positive allosteric modulators, along with the progress in structure-activity relationship studies on both orthosteric and allosteric scaffolds to offer pathways for future therapeutics to this novel biological target for neuropsychiatric disorders.

Aripiprazole alleviates the high prolactin levels induced by amisulpride via distinct molecular mechanisms: a network pharmacology and molecular docking study

BackgroundAmisulpride, a unique atypical antipsychotic, significantly increases prolactin secretion during schizophrenia treatment, resulting in adverse effects that reduce patient quality of life and treatment adherence. Aripiprazole, a partial dopamine D2 receptor agonist, reduces prolactin elevation induced by antipsychotic drugs used for schizophrenia treatment. The molecular targets and mechanisms underlying the contrasting effects of these two drugs on prolactin regulation are unclear. The objective of this study was to systematically explore the molecular mechanisms of prolactin regulation by aripiprazole and amisulpride using network pharmacology and molecular docking techniques.MethodsRelevant targets of amisulpride and aripiprazole and for schizophrenia and elevated prolactin treatment were obtained from online databases and screened for significance. A protein-protein interaction network was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of the core targets were performed to identify key biological processes and signaling pathways, and a target-pathway-drug integrated network was established. The binding affinities of amisulpride and aripiprazole with core targets were predicted using molecular docking analyses.ResultsScreening and matching drug and disease targets combined with GO and KEGG pathway enrichment analyses revealed several key signaling pathways involved in prolactin regulation, including MAPK, PI3K/AKT, and dopamine receptor pathways. The core targets of aripiprazole include MAPK3, PPARG, DRD2, and ESR1, and amisulpride primarily targets MMP9, CDC42, mTOR, and AKT1. Molecular docking analysis demonstrated that aripiprazole and amisulpride have high binding affinities for their respective targets, supporting the hypothesis that these drugs regulate prolactin levels through target-ligand interactions.ConclusionThese findings highlight the distinct signaling pathways and molecular networks involved in prolactin regulation by aripiprazole and amisulpride and provide new insights into the mechanisms of these drugs in schizophrenia treatment. Further pharmacological and clinical research is needed to validate the complex regulatory networks and in vivo effects.

From theory to therapy: unlocking the potential of muscarinic receptor activation in schizophrenia with the dual M1/M4 muscarinic receptor agonist xanomeline and trospium chloride and insights from clinical trials.

Since the 1950s, understanding of antipsychotic activity in schizophrenia has been largely grounded in the dopamine (DA) hypothesis. Most antipsychotics approved for schizophrenia interact with D2 DA receptors as an important part of their mechanism of action. While antipsychotics blocking D2 DA receptors can be effective for positive symptoms of schizophrenia, none are approved by regulatory authorities for predominant negative or cognitive symptoms. Moreover, many of these agents induce a range of problematic side effects related to D2 DA receptor blockade (eg, drug-induced parkinsonism, akathisia, tardive dyskinesia, hyperprolactinemia and related sexual side effects, sedation). This has prompted the search for novel mechanisms with improved efficacy and tolerability based on evidence supporting involvement of other neurotransmitter systems in schizophrenia pathophysiology, including acetylcholine, gamma-aminobutyric acid, and glutamate. Among these options, targeting muscarinic receptors emerged as a promising treatment strategy. In September 2024, the U.S. Food and Drug Administration approved xanomeline and trospium chloride for treatment of adults with schizophrenia based on results from three 5-week, randomized, double-blind, placebo-controlled trials and two 52-week open-label trials. In the placebo-controlled trials, xanomeline/trospium reduced symptoms of schizophrenia, was generally well tolerated, and was not associated with clinically meaningful motor symptoms, hyperprolactinemia, sexual side effects, or weight gain compared with placebo. The long-term safety of xanomeline/trospium was also confirmed in two 52-week, open-label trials. This paper reviews the preclinical and clinical rationale for muscarinic receptor activation as a treatment for schizophrenia and the efficacy, safety, and tolerability profile of xanomeline/trospium.

Levodopa treatment: impacts and mechanisms throughout Parkinson's disease progression.

Treatment with levodopa, a precursor of dopamine (DA), to compensate for the loss of endogenous DA in Parkinson's disease (PD), has been a success story for over 50years. However, in late stages of PD, the progressive degeneration of dopaminergic neurons and the ongoing reduction in endogenous DA concentrations make it increasingly difficult to maintain normal-like DA function. Typically, in late PD, higher doses of levodopa are required, and the fluctuations in striatal DA concentrations-reflecting the timing pattern of levodopa administrations-become more pronounced. These DA fluctuations can include highs that induce involuntary movements (levodopa-induced dyskinesia, LID) or lows that result in insufficient suppression of PD symptoms ("OFF" phases). The enhanced fluctuations primarily arise from the loss of DA buffering capacity, resulting from the degeneration of DA neurons, and an increased reliance on levodopa-derived DA release as a "false neurotransmitter" by serotonergic neurons. In many patients, the LID and OFF-phases can be alleviated by modifying the levodopa therapy to provide a more continuous delivery or by using additional medications, such as monoamine oxidase-B (MAO-B) inhibitors, amantadine, or dopaminergic receptor agonists. Understanding the challenges faced by levodopa therapy also requires considering that the PD striatum is characterized not only by the loss of DA neurons but also by neuroplastic adaptations and PD-induced degenerations of other neural populations. This review provides a broad overview on the use of levodopa in treating PD, with a focus on the underlying science of the challenges encountered in late stages of the disease.

Computational Investigation of Montelukast and Its Structural Derivatives for Binding Affinity to Dopaminergic and Serotonergic Receptors: Insights from a Comprehensive Molecular Simulation

Background/Objectives: Montelukast (MLK), a leukotriene receptor antagonist, has been associated with neuropsychiatric side effects. This study aimed to rationally modify MLK’s structure to reduce these risks by optimizing its interactions with dopamine D2 (DRD2) and serotonin 5-HT1A receptors using computational molecular simulation techniques. Methods: A library of MLK derivatives was designed and screened using structural similarity analysis, molecular docking, molecular dynamics (MD) simulations, MM/PBSA binding free energy calculations, and ADME-Tox predictions. Structural similarity analysis, based on Tanimoto coefficient fingerprinting, compared MLK derivatives to known neuropsychiatric drugs. Docking was performed to assess initial receptor binding, followed by 100 ns MD simulations to evaluate binding stability. MM/PBSA calculations quantified binding affinities, while ADME-Tox profiling predicted pharmacokinetic and toxicity risks. Results: Several MLK derivatives showed enhanced DRD2 and 5-HT1A binding. MLK_MOD-42 and MLK_MOD-43 emerged as the most promising candidates, exhibiting MM/PBSA binding free energies of −31.92 ± 2.54 kcal/mol and −27.37 ± 2.22 kcal/mol for DRD2 and −30.22 ± 2.29 kcal/mol and −28.19 ± 2.14 kcal/mol for 5-HT1A, respectively. Structural similarity analysis confirmed that these derivatives share key pharmacophoric features with atypical antipsychotics and anxiolytics. However, off-target interactions were not assessed, which may influence their overall safety profile. ADME-Tox analysis predicted improved oral bioavailability and lower neurotoxicity risks. Conclusions: MLK_MOD-42 and MLK_MOD-43 exhibit optimized receptor interactions and enhanced pharmacokinetics, suggesting potential neuropsychiatric applications. However, their safety and efficacy remain to be validated through in vitro and in vivo studies. Until such validation is performed, these derivatives should be considered as promising candidates with optimized receptor binding rather than confirmed safer alternatives.

A Wireless Cortical Surface Implant for Diagnosing and Alleviating Parkinson's Disease Symptoms in Freely Moving Animals.

Parkinson's disease (PD), one of the most common neurodegenerative diseases, is involved in motor abnormality, primarily arising from the degeneration of dopaminergic neurons. Previous studies have examined the electrotherapeutic effects of PD using various methodological contexts, including live conditions, wireless control, diagnostic/therapeutic aspects, removable interfaces, or biocompatible materials, each of which is separately utilized for testing the diagnosis or alleviation of various brain diseases. Here, a cortical surface implant designed to improve motor function in freely moving PD animals is presented. This implant, a minimally invasive system equipped with a graphene electrode array, is the first integrated system to exhibit biocompatibility, wearability, removability, target specificity, and wireless control. The implant positioned at the motor cortical surface activates the motor cortex to maximize therapeutic effects and minimize off-target effects while monitoring motor activities. In PD animals, cortical motor surface stimulation restores motor function and brain waves, which corresponds to potentiated synaptic responses. Furthermore, these changes are associated with the upregulation of metabotropic glutamate receptor 5 (mGluR5, Grm5) and D5 dopamine receptor (D5R, Drd5) genes in the glutamatergic synapse. The newly designed wireless neural implant demonstrates capabilities in both real-time diagnostics and targeted therapeutics, suggesting its potential as a wireless system for biomedical devices for patients with PD and other neurodegenerative diseases.

Astaxanthin Mitigates ADHD Symptoms in Spontaneously Hypertensive Rats via Dopaminergic Modulation and Brain–Gut Axis Regulation

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that significantly impacts learning, daily functioning, and personal development. Astaxanthin (ASTA), a naturally occurring antioxidant, has garnered interest as a potential therapeutic agent for various diseases, particularly in mitigating oxidative stress. This study explores a novel application of ASTA in the context of ADHD, aiming to investigate its therapeutic effects and underlying mechanisms. Spontaneously hypertensive rats (SHRs), widely used ADHD model animals, were treated with ASTA (50/100 mg/kg/day) for three weeks, 5 mg/kg/day atomoxetine (ATO) as the positive, and Wistar Kyoto (WKY) rats as control. Behavioral improvements were assessed using the open field test (OFT) and the Morris water maze (MWM). Biochemical analyses were conducted to evaluate changes in the levels of various neurotrophic factors, while histological examinations were performed to assess neuroprotective effects. Additionally, the role of ASTA in the brain–gut axis was investigated. The behavioral symptoms of hyperactivity, anxiety, and impaired spatial memory in ADHD animals were mitigated by ASTA. This improvement is primarily attributed to the restoration of neurotransmitter levels, particularly dopamine (DA), achieved through the modulation of several critical components within the dopamine system, including dopamine receptor 1 (DR1), dopamine transporter (DAT), tyrosine hydroxylase (TH), and synaptic-associated protein 25 (SNAP-25). Additionally, regulating the serotonin transporter (SERT) and glial cell-derived neurotrophic factor (GDNF) supports the recovery of serotonin levels and facilitates optimal brain development. Furthermore, cerebellar cells were protected, and the structure of the intestinal microbiota was regulated. ASTA can mitigate ADHD symptoms in SHR through the modulation of the dopaminergic system, multiple neurotransmitters, neurotrophic factors, and the neuro-intestinal environment, which establishes ASTA as a promising nutraceutical candidate for adjunctive therapy in pediatric ADHD.

Estimating Brain Similarity Networks with Diffusion MRI.

Structural similarity has emerged as a promising tool in mapping the network organization of an individual, living human brain. Here, we propose diffusion similarity networks (DSNs), which employ rotationally invariant spherical harmonic features derived from diffusion magnetic resonance imaging (dMRI), to map gray matter structural organization. Compared to prior approaches, DSNs showed clearer laminar, cytoarchitectural, and micro-architectural organization; greater sensitivity to age, cognition, and sex; higher heritability in a large dataset of healthy young adults; and straightforward extension to non-cortical regions. We show DSNs are correlated with functional, structural, and gene expression connectomes and their gradients align with the sensory-fugal and sensorimotor-association axes of the cerebral cortex, including neuronal oscillatory dynamics, metabolism, immunity, and dopaminergic and glutaminergic receptor densities. DSNs can be easily integrated into conventional dMRI analysis, adding information complementary to structural white matter connectivity, and could prove useful in investigating a wide array of neurological and psychiatric conditions.

Bioelectric Membrane Potential and Breast Cancer: Advances in Neuroreceptor Pharmacology for Targeted Therapeutic Strategies

Bioelectric membrane potentials regulate cellular growth, differentiation, and movement. Disruptions in bioelectric signaling are strongly linked to cancer development, as abnormal membrane potentials and ion channel activity can drive tumor progression. In breast cancer, ion channel dysfunction and neuroreceptor-related pathways play significant roles in the cell cycle, epithelial–mesenchymal transition, angiogenesis, inflammation, the tumor microenvironment, and tumor progression. Neuroreceptors are critical not only in initiating and advancing cancer but also in conferring resistance to treatments. Neuroreceptors also play a key role, with dopamine receptor D2 activation reducing breast tumor growth by 40% in preclinical models, while serotonin signaling has been shown to promote epithelial–mesenchymal transition (EMT), increasing invasiveness. Advances in understanding these biological mechanisms could lead to more cost-effective and less invasive therapeutic strategies to treat tumors. This review explores the expanding evidence connecting bioelectric activity to breast cancer, focusing on neuroreceptor pharmacology as a transformative therapeutic approach. Examining the modulation of bioelectricity through neuroreceptor pharmacology to influence breast cancer progression and integrating these insights into therapeutic development offers a promising path for addressing treatment challenges and improving precision in managing aggressive cancer subtypes.

Role of dopamine receptor heteromerization in preclinical models of addiction and other psychiatric disorders

Similar to other psychiatric disorders, drug addiction is linked to changes in neuronal activity within the mesolimbic system, which consists of dopamine (DA) neurons of the ventral tegmental area projecting to the ventral part of the striatum, the nucleus accumbens (NAc). All drugs of abuse indeed artificially increase DA concentration in the NAc, which hijacks the reward system and triggers lasting behavioral alterations, including compulsive drug-seeking and drug-taking behavior despite negative consequences and a high rate of relapse after abstinence. DA chiefly signals through DA receptor (DAR) type 1 (D1R) and type 2 (D2R), which are G protein-coupled receptor (GPCR) that are positively and negatively coupled to adenyl cyclase, respectively. Multiple evidence indicates that the potent modulatory roles of DA on other neurotransmitters and neuromodulator systems implicate the direct physical interactions (i.e., heteromerization) of DAR with other receptors. DAR heteromerization, which is increased in several preclinical models of psychiatric disorders, leads to a reciprocal and fine-tuned modulation of DAR and partner receptors, therefore suggesting that targeting DAR heteromerization may contribute to the development of clinically relevant strategies. Herein, we provide an overview of current methodologies used for detecting receptor heteromers both in heterologous systems and in situ in the brain and discuss their respective advantages and limitations. We also argue that D1R and D2R have been shown to form heteromers with multiple partner receptors in heterologous systems but only few studies were able to a provide proof of their existence in the brain or establish their biological roles. This review will emphasize on studies describing the modulation and functions of DAR heteromerization in the brain in preclinical models of psychiatric disorders, with a particular focus on addiction, a field in which those heteromerization processes have been the most extensively studied.

Reduced sensitivity to cocaine effects and changes in mesocorticolimbic dopamine receptors in adolescent sexually active female rats.

The sexual behavior of the female rat is highly motivated, and the mesocorticolimbic dopaminergic system -involved in psychostimulants effects- has been implicated in its regulation. Female rats begin to express sexual behavior during adolescence, a period during which this system is not yet mature. To examine the impact of cocaine on sexual motivation and behavior of adolescent and adult female rats, and to determine the dopamine receptors binding in mesocorticolimbic areas of these females. The effect of acute administration of cocaine (0.0, 10.0, and 20.0mg/kg, intraperitoneally) on the male´s incentive value for females and on their sexual behavior in late adolescent (45-55days old) and adult (100-120days old) rats was assessed during late proestrus. The binding of D1-like and D2-like receptors in the striatum and medial prefrontal cortex (mPFC) of adolescent and adult rats were determined by autoradiography. Cocaine did not affect females´ preference for the male. However, 10mg/kg of cocaine reduced the expression of sexual motivated responses and 20mg/kg also diminished sexual receptivity exclusively in adult subjects. Moreover, cocaine-induced a more pronounced hyper-locomotion in adult than in late adolescent rats. Late adolescent females exhibited higher dopamine receptors binding in the mPFC and reduced D2-like receptors binding in the Nucleus Accumbens shell when compared to adults. Late adolescent females are less sensitive than adults to the detrimental effects of cocaine on sexual behavior and locomotion. This phenomenon is accompanied by variation in dopamine receptors in mesocorticolimbic areas affected by this psychostimulant.

Nigella sativa oil modulates neurobehavioral and neurochemical alterations in alcohol-exposed rats: An in vivo and in silico study.

Nigella sativa oil modulates neurobehavioral and neurochemical alterations in alcohol-exposed rats: An in vivo and in silico study.

Frontispiece: Fluorescent Artificial Receptor for Dopamine based on Molecular Recognition‐driven Dynamic Covalent Chemistry in a Lipid Nanoreactor

Frontispiece: Fluorescent Artificial Receptor for Dopamine based on Molecular Recognition‐driven Dynamic Covalent Chemistry in a Lipid Nanoreactor