Open research questions in Neurotransmitter Receptor Influence on Behavior

What the literature leaves open

• well-powered, prospective clinical studies investigating uPA concentrations and activity, - determining whether uPA measures are associated with prospectively assessed clinical outcomes, - directly determining whether manipulation of uPA-or tPA-dependent BDNF processing alters synaptic plasticity and drug-related behavioural outcomes

  Novel Roles of Urokinase- and Tissue-Type Plasminogen Activators in Substance Use Disorders: A Narrative Review of Molecular Mechanisms and Translational Perspectives · 2026 · DOI

• Investigate the role of CP-AMPARs in other brain regions, - Examine the effects of CP-AMPARs on other substances, - Study the mechanisms underlying the sex difference in CP-AMPAR contribution to motivation, - Explore the potential of CP-AMPAR antagonists as treatments for substance use disorders

  Calcium-permeable AMPA receptors contribute to the accelerated development of enhanced motivation for cocaine in female rats · 2026 · DOI

• There is a lack of understanding about the long-term neurobiological ramifications of methamphetamine use in humans. The effects of methamphetamine on the human brain, particularly in the context of inhibitory processing, are not well studied.

  Substance-related visual cues alter sensory gating in adults who regularly use methamphetamine · 2026 · DOI

• The development of targeted therapies for methamphetamine use disorder is impeded by the poor characterization of its neurobiological mechanisms. The integration of advanced morphometric techniques and network-level analyses is limited. The analysis of structural covariance networks and cortical thickness requires specialized software and expertise.

  Altered morphological cortical thickness and disrupted network attributes and its relationships with drug use characteristics and impulsivity in abstinent male subjects with methamphetamine use disorder · 2025 · DOI

• The limited integration of advanced morphometric techniques and network-level analyses to unravel how structural reorganization mediates behavioral pathologies in methamphetamine use disorder. The incomplete understanding of the associations between methamphetamine addiction, trait impulsivity, and neurobiological mechanisms.

  Altered morphological cortical thickness and disrupted network attributes and its relationships with drug use characteristics and impulsivity in abstinent male subjects with methamphetamine use disorder · 2025 · DOI

• Further studies are needed to explore the role of placental serotonergic signaling in fetal brain development, - Studies should investigate the effects of placental serotonergic system dysregulation on infant neurodevelopmental outcomes, - Research should examine the relationship between placental 5-HT levels and neurodevelopmental processes

  Placental serotonergic system dysregulation is associated with early impairments in infant neurodevelopment · 2025 · DOI

• Further research is needed to understand the long-term neurobiological ramifications of methamphetamine use in humans, - Studies should investigate the effects of methamphetamine use on brain function in different populations, - Research should examine the relationship between methamphetamine use and other psychiatric symptoms

  Substance-related visual cues alter sensory gating in adults who regularly use methamphetamine · 2026 · DOI

• The molecular basis of the telescoping effect remains unknown. The neurobiological mechanisms driving the accelerated trajectory in females are poorly understood.

  Calcium-permeable AMPA receptors contribute to the accelerated development of enhanced motivation for cocaine in female rats · 2026 · DOI

• Dysregulation of this balance is implicated in neuropsychiatric disease, and while sex differences in this balance have been described, the biological bases remain unclear.

  Sex differences in exploration-exploitation strategies during home-cage decision making · 2026 · DOI

• It is usually assumed that they index a common underlying trait, yet few studies have investigated this in a large group of male and female mice using an advanced analytical approach.

  Convergent activity but divergent anxiety dimensions in male and female C57BL/6 mice across the open field and elevated plus maze · 2026 · DOI

• Real-time fMRI neurofeedback can modify clinically relevant brain states, but transferring brain dynamics between peers has not been tested, particularly in addiction, where social learning is central to recovery.

  Peer-guided movie neurofeedback to facilitate recovery in opioid use disorder · 2026 · DOI

• Among these, the gut-brain vagal axis has emerged as a key regulator, although its precise contribution to mesolimbic DA signaling and behavior remains unclear.

  The gut-brain vagal axis governs mesolimbic dopamine dynamics and reward events · 2026 · DOI

• Evidence suggests that their special properties lie at the functional core of neural tissue, but the dynamics of serotonin in the extracellular space remain poorly understood because of major experimental limitations on the relevant (sub-micrometer/millisecond) scales.

  Compartmental-Reaction Diffusion Framework for Microscale Dynamics of Extracellular Serotonin in Brain Tissue · 2026 · DOI

• Clinically, motivational deficits are linked to psychiatric disorders such as depression and schizophrenia, yet the neural mechanisms by which aversive contexts suppress motivation remain unclear.

  Motivation under aversive conditions is regulated by a striatopallidal pathway in primates · 2026 · DOI

• Monoamines such as serotonin, dopamine, and tyramine regulate physiological and behavioral processes in bilaterian animals, but the evolutionary origin of the monoaminergic system remains unclear.

  Prebilaterian origin of monoaminergic signaling · 2026 · DOI

• Previous studies suggest that Meth-induced behavioral and neuronal dysfunctions are different between males and females, but the cellular and molecular mechanism are not fully understood.

  Methamphetamine self-administration causes neuronal dysfunction in rat medial prefrontal cortex in a sex-specific and withdrawal time-dependent manner · 2025 · DOI

• However, little is known about the influence of placental serotonergic components on early neurodevelopmental outcomes.

  Placental serotonergic system dysregulation is associated with early impairments in infant neurodevelopment · 2025 · DOI

• Dopamine and gamma-aminobutyric acid (GABA) neurons in the ventral tegmental area (VTA) are implicated in reward and punishment learning, yet little is known about how each population adapts when the predicted outcome valence changes.

  Flexible updating of reward and punishment contingencies by VTA GABA neurons · 2025 · DOI

• Although these alterations have been well documented in various forms of SUD, the electrophysiological mechanisms specific to opioid use disorder (OUD) remain underexplored.

  Processing abnormalities in monetary outcome evaluations among male individuals with opioid use disorder: evidence from feedback-related negativity · 2024 · DOI

• Whilst reward pathologies are major and common in stress-related neuropsychiatric disorders, their neurobiology and treatment are poorly understood.

  Chronic stress deficits in reward behaviour co-occur with low nucleus accumbens dopamine activity during reward anticipation specifically · 2024 · DOI

• Building upon a valuable yet limited evidence base, we suggest the next challenge in enhancing monitoring, personalized assessment, and therapy for addiction is to refine neurocognitive assessment protocols.

  Integrating EEG biomarkers in the neurocognitive screening of executive functions in substance and behavioral addiction · 2024 · DOI

• Although current evidence in mental health is limited, these neighbouring studies suggest novel opportunities that could and should be validated and implemented soon.

  Integrating EEG biomarkers in the neurocognitive screening of executive functions in substance and behavioral addiction · 2024 · DOI

• However, useful transdiagnostic models that could integrate clinical evaluation derived from neuroscientific theories are lacking.

  Proposing an integrative, dynamic and transdiagnostic model for addictions: dysregulation phenomena of the three main modes of the predostatic mind · 2024 · DOI

• There is a lack of research into the effects of adolescent binge-like exposure to ethanol and cannabinoids in chronically nicotine-treated rats. There is a need for further research into the persistent sex-dependent effects in adulthood.

  Sex-specific behavioral and monoaminergic network alterations following adolescent binge-like ethanol and WIN55,212-2 exposure under chronic nicotine in rats · 2026 · DOI

• Repeated testing can affect novelty driven behaviors through habituation or one trial tolerance (File and Wardill, 1975; Carobrez and Bertoglio, 2005; Walf and Frye, 2007), the long inter-test interval (30 days) and the inclusion of age and sex matched control groups tested at identical time points likely minimized these effects (Schrader et al., 2018). Moreover, repeated gavage administration may also have induced mild procedural stress, potentially reducing baseline sex differences, in females (Luine et al., 2007), and engaging particularly monoaminergic circuits in stress related allostatic adaptations (Koob and Le Moal, 2001; Koob, 2008). involved The behavioral correlates of the polydrug protocol observed here are subtle. One possible explanation is that they are not readily detectable using conventional quantitative analyses, thus requiring more sensitive multivariate approaches.

  Sex-specific behavioral and monoaminergic network alterations following adolescent binge-like ethanol and WIN55,212-2 exposure under chronic nicotine in rats · 2026 · DOI

Most-cited papers in Neurotransmitter Receptor Influence on Behavior

• Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants · Science · 2003 · 3,580 citations
• Multiple receptors for dopamine · Nature · 1979 · 3,129 citations
• Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5 · Nature · 1986 · 2,729 citations
• The Neural Basis of Addiction: A Pathology of Motivation and Choice · American Journal of Psychiatry · 2005 · 2,186 citations
• Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics · Nature · 1990 · 2,159 citations
• Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex · American Journal of Psychiatry · 2002 · 2,133 citations
• A psychomotor stimulant theory of addiction. · Psychological Review · 1987 · 2,109 citations
• Drug Abuse: Hedonic Homeostatic Dysregulation · Science · 1997 · 1,939 citations
• The adolescent brain · Developmental Review · 2008 · 1,617 citations
• Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls. · Journal of Experimental Psychology General · 1999 · 1,599 citations

Most recent work

• The gut-brain vagal axis governs mesolimbic dopamine dynamics and reward events · Science Advances · 2026
• Single-nucleus transcriptomics reveals cell type-specific and time-dependent effects of psilocybin and ketamine on gene expression · bioRxiv · 2026
• Neurotransmitter dysregulation in depression, anxiety, and suicidality: From synaptic dysfunction to cellular pathogenesis · Psychiatry Research · 2026
• Thalamo-accumbal circuit adaptations following extended oxycodone abstinence. · bioRxiv · 2026
• Alcohol disrupts long-term potentiation at hippocampus-medium spiny neuron synapses in the medial shell of the nucleus accumbens · bioRxiv · 2026
• Male sexual dysfunction associated with selective serotonin reuptake inhibitors (SSRIs): A pharmacovigilance disproportionality analysis of FAERS data · Journal of Affective Disorders · 2026
• Sex differences in insular cortex function in persistent alcohol drinking despite aversion in mice · Molecular Psychiatry · 2026
• Stimulus-dependent dopamine dynamics from locus coeruleus axons · Cell Reports · 2026
• VTA dopamine neuron activity produces spatially organized stimulus and action value representations through conditioned reinforcement · bioRxiv · 2026
• Motivation under aversive conditions is regulated by a striatopallidal pathway in primates · Current Biology · 2026

Related topics in Neuroscience