About

Stephan Anagnostaras is an Associate Professor in the Department of Psychology at UC San Diego. His research laboratory aims to understand how the brain produces behavior and cognition by integrating molecular-genetic, systems, and cognitive-behavioral levels of analysis. Working primarily with mice, his research focuses on three main areas: memory consolidation and the substrates of permanent memory, particularly how hippocampus-dependent memory is transformed and stored over extended periods; fear and anxiety, including fear memory and the genetic contributions to these emotional responses; and memories governing addiction, specifically the role of 'memory genes' in stimulant sensitization. A related line of research investigates the role of genetics in exceptional memory and intelligence. His work seeks to elucidate the interplay of genes, neural systems, behavior, and cognition in the production of memory.

Research topics

• Neuroscience
• Psychology
• Computer Science
• Cell biology
• Pharmacology
• Acoustics
• Biochemistry
• Physics
• Psychiatry
• Biology
• Medicine

Selected publications

• Common Psychostimulants Impair Gross Motor Coordination (Abstract ID: 224454)

  Journal of Pharmacology and Experimental Therapeutics · 2026-05-01

  articleSenior author
  PublisherDOI

• Systematic Dose-Response Analysis of LSD and Evaluation of Its Effects in Addiction-Related Behaviors (Abstract ID: 234062)

  Journal of Pharmacology and Experimental Therapeutics · 2026-05-01

  articleSenior author
  PublisherDOI

• Behavioral impairments are linked to neuroinflammation in mice with Cerebral Cavernous Malformation disease

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-05-31

  preprintOpen accessCorresponding

  Abstract Background Cerebral Cavernous Malformations (CCMs) are neurovascular abnormalities in the central nervous system (CNS) caused by loss of function mutations in KRIT1 (CCM1), CCM2, or PDCD10 (CCM3) genes. One of the most common symptoms in CCM patients is associated with motor disability, weakness, seizures, stress, and anxiety, and the extent of the symptom or symptoms may be due to the location of the lesion within the CNS or whether multiple lesions are present. Previous studies have primarily focused on understanding the pathology of CCM using animal models. However, more research has yet to explore the potential impact of CCM lesions on behavioral deficits in animal models, including effects on short-term and long-term memory, motor coordination, and function. Methods We used the accelerating RotaRod test to assess motor and coordination deficits. We also used the open field test to assess locomotor activity and pathology-related behavior and Pavlovian fear conditioning to assess short—and long-term memory deficits. Our behavioral studies were complemented by proteomics, histology, immunofluorescence, and imaging techniques. We found that neuroinflammation is crucial in behavioral deficits in male and female mice with neurovascular CCM lesions ( Slco1c1-iCreERT2; Pdcd10 fl/fl ; Pdcd10 BECKO ). Results Functional behavior tests in male and female Pdcd10 BECKO mice revealed that CCM lesions cause sudden motor coordination deficits associated with the manifestation of profound neuroinflammatory lesions. Our findings indicate that maturation of CCM lesions in Pdcd10 BECKO mice also experienced a significant change in short- and long-term memory compared to their littermate controls, Pdcd10 fl/fl mice. Proteomic experiments reveal that as CCM lesions mature, there is an increase in pathways associated with inflammation, coagulation, and angiogenesis, and a decrease in pathways associated with learning and plasticity. Therefore, our study shows that Pdcd10 BECKO mice display a wide range of behavioral deficits due to significant lesion formation in their central nervous system and that signaling pathways associated with neuroinflammation and learning impact behavioral outcomes. Conclusions Our study found that CCM animal models exhibited behavioral impairments such as decreased motor coordination and amnesia. These impairments were associated with the maturation of CCM lesions that displayed a neuroinflammatory pattern.

  PublisherOA PDFDOI

• Effect of Methylphenidate on Motor Skill Learning and Consolidation

  Journal of Pharmacology and Experimental Therapeutics · 2023-05-18

  articleOpen accessSenior author
  PublisherOA PDFDOI

• MDMA and memory, addiction, and depression: dose-effect analysis

  Psychopharmacology · 2022 · 33 citations

  Senior authorCorresponding
  • Psychology
  • Pharmacology
  • Medicine

  RATIONALE: ±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that shows substantial promise as a psychotherapeutic agent. Still, there is some concern regarding its behavioral toxicity, and its dose-effect relationship is poorly understood. We previously explored the role of dose in the cognitive effects of MDMA in a systematic review of existing literature and found no evidence in animals that MDMA impairs memory at low doses (< 3 mg/kg) but mixed results at high doses (≥ 3 mg/kg). Since this review comprised mostly of single-dose studies and an assortment of methodologies, an empirical dose-ranging study on this topic is warranted. OBJECTIVES: The current study aims to evaluate the conclusion from our systematic review that 3 mg/kg may be the threshold for MDMA-induced amnesia, and to further understand the dose-effect relationship of MDMA on behavioral assays of memory, addiction, and depression. METHODS: We systematically examined the effects of 0.01 to 10 mg/kg MDMA on Pavlovian fear conditioning; behavioral sensitization, conditioned place preference, and conditioned responding; and the Porsolt forced swim test in mice. RESULTS: High doses of MDMA (≥ 3 mg/kg) produced amnesia of fear conditioning memory, some evidence of an addictive potential, and antidepressant effects, while low doses of MDMA (≤ 1 mg/kg) had no effect on these behaviors. CONCLUSIONS: The present dose-ranging study provides further evidence that 3 mg/kg is the threshold for MDMA-induced amnesia. These findings, in addition to our systematic review, demonstrate that careful selection of MDMA dose is critical. High doses (≥ 3 mg/kg) should likely be avoided due to evidence that they can produce amnesia and addiction. Conversely, there is little evidence to suggest that low doses, which are usually administered in clinical studies (approximately 1-2 mg/kg), will lead to these same adverse effects. Ultra-low doses (< 1 mg/kg) are likely even safer and should be investigated for therapeutic effects in future studies.

  PublisherOA PDFDOI

• Correction to: MDMA and memory, addiction, and depression: dose-effect analysis

  Psychopharmacology · 2022-04-19 · 1 citations

  erratumOpen accessSenior author
  PublisherOA PDFDOI

• Altered Phosphorylation of the Proteasome Subunit Rpt6 Has Minimal Impact on Synaptic Plasticity and Learning

  eNeuro · 2021 · 9 citations

  • Cell biology
  • Biology
  • Neuroscience

  , we created two mouse models which feature mutations at S120 that block or mimic phosphorylation at this site. We find that peptidase and ATPase activities are upregulated in the phospho-mimetic mutant and downregulated in the phospho-dead mutant [S120 mutated to aspartic acid (S120D) or alanine (S120A), respectively]. Surprisingly, these mutations had no effect on basal synaptic transmission, long-term potentiation (LTP), and dendritic spine dynamics and density in the hippocampus. Furthermore, these mutants displayed no deficits in cued and contextual fear memory. Thus, in a mouse model that blocks or mimics phosphorylation at this site, either compensatory mechanisms negate these effects, or small variations in proteasome activity are not enough to induce significant changes in synaptic structure, plasticity, or behavior.

  PublisherOA PDFDOI

• Quantifying the Acoustic Startle Response in Mice Using Standard Digital Video

  Frontiers in Behavioral Neuroscience · 2020 · 36 citations

  Senior authorCorresponding
  • Computer Science
  • Computer Science
  • Psychology

  The startle response is an unconditional reflex, characterized by the rapid contraction of facial and skeletal muscles, to a sudden and intense startling stimulus. It is an especially useful tool in translational research for its consistency across species, simple neural circuitry, and sensitivity to a variety of experimental manipulations. The rodent acoustic startle response is commonly used to study fundamental properties of the central nervous system, including habituation, sensitization, classical conditioning, fear and anxiety, sensorimotor gating, and drug effects. The rodent startle response is typically assessed in stabilimeter chambers, and while these systems are excellent at measuring startle, they are designed only for this sole purpose. In the present study, we used the VideoFreeze system-a widely used tool for studying Pavlovian fear conditioning-to assess the acoustic startle response in freely moving mice. We validated the use of this system to quantify startle response amplitude and prepulse inhibition of startle. This is the first demonstration to date of using standard video in the automated assessment of the acoustic startle response in rodents. We believe that researchers already using the VideoFreeze system will benefit from the additional ability to assess startle without the purchase of new equipment.

  PublisherDOI

• MDMA and Pavlovian Fear Memory: Dose‐Effect Analysis

  The FASEB Journal · 2020-04-01

  articleSenior author

  ±3,4‐methylenedioxymethamphetamine (MDMA) is a recreational drug that is also being pursued as a therapeutic for PTSD and other mood and anxiety disorders. Despite strong evidence of its therapeutic potential, these pursuits are hindered by evidence that MDMA produces robust neurotoxicity and cognitive deficits at high doses. These findings, however, may not generalize to typical recreational or therapeutic use of low‐dose MDMA. To date, there is little research on the cognitive effects of low/moderate doses of MDMA (less than 3 mg/kg) – the doses that users typically take. In the present study, we examined the effects of MDMA on learning and memory across a range of doses using a Pavlovian fear conditioning paradigm. Hybrid C57BL/6Jx129S1/SvImJ mice were randomly assigned to groups by MDMA dose. Mice were trained on‐drug with a single tone‐shock pairing and then tested off‐drug one week later for long‐term context and tone fear memory. We assessed the effects of doses of 0.1 to 8 mg/kg MDMA relative to vehicle control on immediate memory and long‐term contextual and cued memory. With increasing interest in therapeutic uses of MDMA, this research will help determine if low doses are therapeutically viable in terms of adverse effects on learning and memory. Support or Funding Information Source Research Foundation (Connection Award to M.M.P.)

  PublisherDOI

• Dopamine and norepinephrine transporter inhibition for long-term fear memory enhancement

  Behavioural Brain Research · 2019-09-30 · 12 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

Recent grants

• NIH Grant R01DA020041

  NIH · $1.5M · 2013

• NIH Grant R03DA016635

  NIH · $76k · 2005

• NIH Grant F32NS010932

  NIH · $111k

Frequent coauthors

• Seiya Miyamoto

  5198 shared

• Jennifer R Sage

  LVMH (France)

  4310 shared

• Stephanie A Carmack

  National Institute on Drug Abuse

  4295 shared

• Robert L. Balster

  3764 shared

• Richard J Beninger

  3760 shared

• Tomek J Banasikowski

  Providence Health Care

  3760 shared

• Sharon Walsh

  University of Cincinnati

  3724 shared

• Malcolm Lader

  3348 shared