Open research questions in Neurotransmitter Receptor Influence on Behavior

What the literature leaves open

• Limited availability of experimental structures of TAAR1. Need for improved methods for optimizing hit rates and affinity maturation.

  Structure based discovery of antipsychotic-like TAAR1 agonists · 2026 · DOI

• There are no FDA-approved treatments for polysubstance use disorder. The current study aims to address this gap by evaluating the effectiveness of two kappa opioid receptor agonists in attenuating fentanyl and cocaine co-use.

  Effects of repeated nalfurafine and VZTK35 treatments on fentanyl/cocaine mixture self-administration in a rat drug-vs.-food choice procedure · 2026 · DOI

• Future investigations into the neural circuits sculpted by chronic binge-like drinking, particularly those governing social motivations like aggression, - Future studies should measure the impact of repeated cycles of DID in defeated, subordinate (i.e., intruder) mouse populations on their vulnerability to acquiring maladaptive affective-like behavioral phenotypes.

  Aggression and repeated alcohol drinking-in-the-dark: dissecting subtypes in outbred mice · 2026 · DOI

• Prior work has not fully examined individual differences in alcohol intake and aggression. The study aims to address this gap by examining individual patterns of alcohol intake over repeated weeks of drinking-in-the-dark with corresponding measures of offensive aggression.

  Aggression and repeated alcohol drinking-in-the-dark: dissecting subtypes in outbred mice · 2026 · DOI

• There is a gap in understanding the role of PKMζ in the PFC in cocaine taking and seeking behaviors. The study aims to investigate the role of PKMζ within this brain region.

  PKMζ in the prefrontal cortex alters cocaine cue-induced reinstatement in a sex-specific manner · 2026 · DOI

• The molecular mechanisms of methadone maintenance therapy (MMT) for heroin addiction remain largely unclear. There is a need to investigate the molecular mechanisms and potential therapeutic targets of MMT. Further research is needed to understand the underlying mechanisms of MMT.

  Methadone maintenance therapy alters the expression of PLK1 and IFIH1 in patients with heroin addiction: a case-control study · 2026 · DOI

• The lack of understanding of the relationship between dopamine receptor sensitivity and the attribution of incentive salience to reward cues. The need to identify the neurobiological mechanisms underlying vulnerability to addiction. The gap in current research on the role of dopamine D1 and D2 receptors in the appetitive effects of cocaine.

  Dopamine receptor sensitivity, cocaine-induced behaviors, and Pavlovian conditioned approach in male rats · 2026 · DOI

• One challenge is the rapid emergence of novel psychoactive substances that circumvent legal control and mimic the effects of established stimulants. Another challenge is the need for timely preclinical evaluation of these substances to understand their abuse potential. The study also faces the challenge of interpreting the complex behavioral effects of 4-Fluoroethylphenidate in rodents.

  Discriminative stimulus, rewarding, and reinforcing effects of 4-Fluoroethylphenidate in rodents · 2026 · DOI

• Prior work has focused on clinical and demographic characteristics, but their explanatory power remains limited. Biological and neurocognitive markers have yielded modest and often non-replicable effects. There is a need to identify patient-specific factors that may shape antidepressant efficacy.

  From uniform pharmacotherapy to precision psychiatry: reinforcement sensitivity associations with SSRI outcomes · 2026 · DOI

• There is a lack of experimental data on the pharmacological effect of fentanyl analogues. The paper identifies a gap in the understanding of the structure modification and biased signaling pathway of MOR. The study aims to address this gap by investigating the pharmacological effect of (±)-trans-3-methylfentanyl and (±)-cis-3-methylfentanyl.

  Pharmacological effect of (±)-trans-3-methylfentanyl and (±)-cis-3-methylfentanyl · 2026 · DOI

• There is a lack of studies investigating the effect of subtle NMDA receptor blockade and allosteric modulation of α5 GABAA receptors on reward-related impulsivity in rats.

  Influences of subtle NMDA receptor blockade and allosteric modulation of α5 GABAA receptors on reward-related impulsivity in rats · 2026 · DOI

• Prior work has not fully elucidated the comparative effects of inactivation and dopamine receptor agents in the dorsomedial and dorsolateral striatum.

  Comparative effects of inactivation and dopamine receptor agents in the dorsolateral and dorsomedial striatum on performance of action sequences in rats · 2026 · DOI

• The study identifies the challenge of understanding the potential benefits and harms of 6-APB due to its increasing popularity and lack of formal behavioral research. The study also identifies the challenge of finding a low-risk therapeutic alternative to MDMA. The study notes the challenge of interpreting the results of 6-APB administration, such as distinguishing between analgesia and ataxia.

  Dose-effect analysis of 6-APB (“Benzofury”) on fear memory, motor behavior, and reward · 2026 · DOI

• There is a lack of formal behavioral research examining the potential harm or benefits of 6-APB. The study aims to fill this gap by establishing a dose-effect curve of 6-APB on various behaviors.

  Dose-effect analysis of 6-APB (“Benzofury”) on fear memory, motor behavior, and reward · 2026 · DOI

• The specific genetic factors driving negative affective symptoms after psychostimulant exposure are unknown. There is a lack of understanding of the genetic basis of behavioral traits associated with negative affective states.

  Variation in cocaine responses across genetically diverse mouse strains · 2026 · DOI

• One challenge is the complexity of the neural mechanisms underlying risk-based decision-making. Another challenge is the need to translate findings from animal models to human populations. The study also faces the challenge of confirming causal relationships between ACC activity and decision-making.

  Chemogenetic inhibition of the anterior cingulate cortex increases safe decision-making in aged mice performing the Iowa Gambling Task · 2026 · DOI

• The gap is the lack of understanding of the specific contribution of mu and kappa opioid receptor signalling to decision making. The paper aims to fill this gap by examining the effects of mu and kappa opioid receptor signalling on decision making.

  Dissecting the contribution of mu and kappa opioid receptor signalling in effort and delay-related cost/benefit decision making · 2026 · DOI

• Limited understanding of predictive individual traits in rats. Limited studies on stress-induced relapse following punishment-invoked abstinence in rats.

  Robust effects of food deprivation as a relapse trigger: comparison to other stressors, and investigation of predictive individual traits in male and female rats · 2026 · DOI

• Future studies could examine the effects of other factors that may influence demand for ethanol, such as stress or social environment. Research could investigate the neural mechanisms underlying the effects of ethanol vapor exposure on demand for ethanol. Studies could explore the generalizability of the results to other populations, such as humans or other animal models.

  Behavioral economic demand for ethanol in Long Evans rats: Influence of choice context, sex, and vapor history · 2026 · DOI

• The extent to which ethanol demand is modulated by alternative reinforcer availability and biological factors remains unstudied in preclinical animal models. Prior work has focused on human studies, with a lack of research in preclinical animal models.

  Behavioral economic demand for ethanol in Long Evans rats: Influence of choice context, sex, and vapor history · 2026 · DOI

• The study only examined the acute effects of ATDs. The study did not investigate the chronic effects of ATDs.

  Acute apocynin-tandospirone derivatives (ATDs) exacerbate methamphetamine-induced hyperlocomotion in rats · 2026 · DOI

• Investigate the chronic effects of ATDs. Examine the effects of ATDs on other behavioral abnormalities.

  Acute apocynin-tandospirone derivatives (ATDs) exacerbate methamphetamine-induced hyperlocomotion in rats · 2026 · DOI

• Further research is needed to investigate the effects of positive modulation of α5GABAA receptors on delay intolerance, - Further research is needed to investigate the effects of MK-801 on cognition and impulsivity, - Further research is needed to investigate the potential of GL-II-73 as a proimpulsive…

  Influences of subtle NMDA receptor blockade and allosteric modulation of α5 GABAA receptors on reward-related impulsivity in rats · 2026 · DOI

• Investigating adaptations within striatal circuits as new skills are mastered, - Examining the role of D2 receptors in the DLS in skilled action…

  Comparative effects of inactivation and dopamine receptor agents in the dorsolateral and dorsomedial striatum on performance of action sequences in rats · 2026 · DOI

• Investigate the effects of ACC inhibition on other types of decision-making tasks, - Examine the neural mechanisms underlying the effects of ACC inhibition on decision-making, - Explore the potential therapeutic applications of ACC inhibition for the treatment of psychopathology-associated cognitive…

  Chemogenetic inhibition of the anterior cingulate cortex increases safe decision-making in aged mice performing the Iowa Gambling Task · 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
• Tirzepatide reduces alcohol drinking and relapse-like behaviours in rodents · EBioMedicine · 2026
• Large-scale behavioral characterization of oxycodone self-administration in heterogeneous stock rats reveals initial analgesic effects are associated with addiction-like behaviors · Neuropsychopharmacology · 2026
• Divergent Roles of Nucleus Accumbens D1- and D2-MSNs in Regulating Hedonic Feeding · Journal of Neuroscience · 2026
• Dopamine Supports Reward Prediction to Shape Reward-Pursuit Strategy · Journal of Neuroscience · 2026
• Sex-Specific patterns of vulnerability to alcohol addiction-like behaviors in rats · Translational Psychiatry · 2026
• The ventral/anterior hippocampus as a central hub for stress-related dopaminergic circuit dysfunction in psychiatric disorders · Molecular Psychiatry · 2026
• Tirzepatide attenuates mesolimbic cocaine-evoked dopamine levels and reduces cocaine taking, motivation and seeking behaviours in male rodents · EBioMedicine · 2026
• Procedural separation of appetitive and consummatory behaviors in operant ethanol self‐administration: A review and open‐source analytical framework · Alcoholism Clinical and Experimental Research · 2026
• Single-nucleus transcriptomics reveals cell type-specific and time-dependent effects of psilocybin and ketamine on gene expression · bioRxiv · 2026

Related topics in Neuroscience