Vanessa Doulames

All Publications

• Hydrogel formulations for sustained-release of broadly neutralizing antibodies. Journal of controlled release : official journal of the Controlled Release Society Jons, C. K., Kasse, C. M., Mayer, B. T., Hyrien, O., Sen, S., Meany, E. L., d'Aquino, A. I., Ganesh, P., Eckman, N., Dong, C., Yan, J., Nguyen, L. T., Doulames, V. M., Song, Y. E., Saouaf, O. M., Williams, C. M., Williams, S. C., Paredes, J., Raghavan, R., Palomares, M., Alpert, M., Yates, N. L., Tomaras, G. D., Seaman, M. S., Farzan, M., Appel, E. A. 2025: 114349

  Abstract

  Sustained serum levels of broadly neutralizing antibodies (bnAbs) are crucial for effective passive immunization against infectious diseases as protection persists only while these bnAbs remain at adequate concentrations within the body. Current obstacles, such as poor pharmacokinetics (PK) and burdensome administration, must be overcome to make bnAbs a viable option for pre- and post-exposure prophylaxis. In this work, we explore how a polymer-nanoparticle (PNP) hydrogel depot technology can be engineered to prolong protein delivery and enable drug exposure on the order of weeks to months. In-vivo studies in mice and rats demonstrate extended protein release compared to bolus administration, and modeling efforts predict the impact of both the elimination half-life of the active pharmaceutical ingredient and hydrogel depot volume on overall pharmacokinetics. Moreover, flow cytometry characterization reveals that immune cell infiltration into the hydrogel depot can result in faster-than-expected release of antibody cargo on account of active transport via cellular uptake. We then demonstrate that co-formulation of antibodies with an anti-inflammatory agent reduces cellular infiltration and resulting active transport, further extending delivery and pharmacokinetics. Finally, multicompartmental modeling predicts the human PK profiles of clinically relevant HIV bnAbs delivered via subcutaneous hydrogel injection. These findings aid in the development of next generation hydrogel materials that stabilize and slowly release bnAbs for long-term pre-exposure immunoprophylaxis.

  View details for DOI 10.1016/j.jconrel.2025.114349

  View details for PubMedID 41177463

• Intranasal Sertraline for the Investigation of Nose-to-Brain Delivery to Mitigate Systemic Exposure. ACS pharmacology & translational science Williams, S. C., Lantz, T., Doulames, V., Alakesh, A., Ramos Mejia, D., Jons, C. K., Huang, Z. Y., Eckman, N., Appel, E. A. 2025; 8 (10): 3669-3676

  Abstract

  Antenatal depression, or depression during pregnancy, is a common psychiatric disorder and poses significant risks to both the mother and the fetus. Despite these risks, it is frequently left untreated due to fears of side effects caused by antidepressant medications which cross through the placental barrier. It is therefore desirable to develop formulation strategies to mitigate systemic exposure to psychotropics while maintaining their efficacy. In this work, we develop formulations of sertraline, a common antidepressant, to target delivery to the brain through intranasal administration. Formulation engineering enables successful solubilization of sertraline at high concentrations over months at room temperature. Using mice, we compare sertraline biodistribution following intranasal administration and standard oral administration. Intranasal administration of our candidate formulation provides comparable brain exposure at half the dose compared to oral treatment and lowers the maximum plasma exposure. These findings suggest that intranasal administration may provide selectivity for drug exposure in the central nervous system over systemic exposure.

  View details for DOI 10.1021/acsptsci.5c00560

  View details for PubMedID 41098574

  View details for PubMedCentralID PMC12519257

• Intranasal Sertraline for the Investigation of Nose-to-Brain Delivery to Mitigate Systemic Exposure ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE Williams, S. C., Lantz, T., Doulames, V., Alakesh, A., Ramos Mejia, D., Jons, C. K., Huang, Z., Eckman, N., Appel, E. A. 2025

  View details for DOI 10.1021/acsptsci.5c00560

  View details for Web of Science ID 001577267800001

• Engineering Sustained-Release Broadly Neutralizing Antibody Formulations. bioRxiv : the preprint server for biology Jons, C. K., Kasse, C. M., Mayer, B. T., Hyrien, O., Sen, S., Meany, E. L., d'Aquino, A. I., Ganesh, P., Eckman, N., Dong, C., Yan, J., Nguyen, L. T., Doulames, V. M., Song, Y. E., Saouaf, O. M., Williams, C. M., Williams, S. C., Paredes, J., Raghavan, R., Palomares, M., Alpert, M., Yates, N. L., Tomaras, G. D., Seaman, M. S., Farzan, M., Appel, E. A. 2025

  Abstract

  Sustained serum levels of broadly neutralizing antibodies (bnAbs) are crucial for effective passive immunization against infectious diseases as protection persists only while these bnAbs remain at adequate concentrations within the body. Current obstacles, such as poor pharmacokinetics (PK) and burdensome administration, must be overcome to make bnAbs a viable option for pre- and post-exposure prophylaxis. In this work, we explore how a polymer-nanoparticle (PNP) hydrogel depot technology can be engineered to prolong protein delivery. In-vivo studies in mice and rats demonstrate prolonged protein release, and modeling efforts predict the impact of both the elimination half-life of the active pharmaceutical ingredient and hydrogel depot volume on overall pharmacokinetics. Moreover, flow cytometry characterization reveals that immune cell infiltration into the hydrogel depot can result in faster-than-expected release of antibody cargo on account of active transport via cellular uptake. We then demonstrate that co-formulation of antibodies with an anti-inflammatory agent reduces cellular infiltration and resulting active transport, further extending delivery and pharmacokinetics. Finally, multicompartmental modeling predicts the human PK profiles of clinically relevant HIV bnAbs delivered via subcutaneous hydrogel injection. These findings aid in the development of next generation hydrogel materials that stabilize and slowly release bnAbs for long-term pre-exposure immunoprophylaxis.

  View details for DOI 10.1101/2025.05.27.656504

  View details for PubMedID 40501883

• Multidirectional alignment of collagen fibers to guide cell orientation in 3D-printed tissue. bioRxiv : the preprint server for biology Singhal, D., Christakopoulos, F., Brunel, L. G., Borkar, S., Doulames, V. M., Myung, D., Fuller, G. G., Heilshorn, S. C. 2025

  Abstract

  Natural tissue comprises fibrous proteins with complex fiber alignment patterns. Here, we develop a reproducible method to fabricate biomimetic scaffolds with patterned fiber alignment along multiple orientations. While extrusion-based approaches are commonly used to align fibrous polymers in a single orientation parallel to the direction of flow, we hypothesized that extrusion-based 3D printing could be utilized to achieve more complex patterns of fiber alignment. Specifically, we show control of lateral spreading of a printed filament can induce fiber alignment that is either parallel or perpendicular to the flow direction. Theoretical prediction of the printing parameters that control fiber orientation was experimentally validated using a collagen biomaterial ink. The velocity ratio of the printhead movement relative to the ink extrusion rate was found to dictate collagen fiber alignment, allowing for the informed fabrication of collagen scaffolds with prescribed patterns of fiber alignment. For example, controlled variation of the ink extrusion rate during a single print resulted in scaffolds with specified regions of both parallel and perpendicular collagen fiber alignment. Human corneal mesenchymal stromal cells seeded onto the printed scaffolds adopted a spread morphology that aligned with the underlying collagen fiber patterns. This technique worked well for filaments either printed into air or extruded within a support bath using embedded 3D printing, enabling the fabrication of 3D structures with aligned collagen fibers. Taken together, this work demonstrates a theoretical and experimental framework to achieve the reproducible fabrication of 3D printed structures with controlled collagen fiber patterns that guide cellular alignment.

  View details for DOI 10.1101/2025.05.20.654730

  View details for PubMedID 40661566

  View details for PubMedCentralID PMC12258732

• Preventing peritendinous adhesions using lubricious supramolecular hydrogels. bioRxiv : the preprint server for biology Meany, E. L., Williams, C. M., Song, Y. E., Doulames, V. M., Bailey, S. J., Williams, S. C., Jons, C. K., Fox, P. M., Appel, E. A. 2025

  Abstract

  Of the 1.5 million emergency room visits each year in the United States due to flexor tendon injuries in the hand, over 30-40% result in peritendinous adhesions which can limit range of motion (ROM) and severely impact an individual's quality of life. Adhesions are fibrous scar-like tissues which can form between adjacent tissues in the body in response to injury, inflammation, or during normal healing following surgery. Currently, there is no widespread solution for adhesion prevention in the delicate space of the digit while allowing a patient full ROM quickly after surgery. There is a clear clinical need for a material capable of limiting adhesion formation which is simple to apply, does not impair healing, remains at the application site during motion and initial inflammation (days - weeks), and leaves tendon glide unencumbered. In this work, we developed dynamically crosslinked, bioresorbable supramolecular hydrogels as easy-to-apply lubricious barriers to prevent the formation of peritendinous adhesions. These hydrogels exhibit excellent long-term stability, injectability, and thermally stable viscoelastic properties that allow for simple storage and facile application. We evaluated interactions at the interface of the hydrogels and relevant tissues, including human tendon and skin, in shear and extensional stress modes and demonstrated a unique mechanism of adhesion prevention based on maintenance of a lubricious hydrogel barrier between tissues. Ex vivo studies show that the hydrogels did not impair the gliding behavior nor mechanical properties of tendons when applied in cadaveric human hands following clinically relevant flexor tendon repair. We further applied these hydrogels in a preclinical rat Achilles tendon injury model and observed prolonged local retention at the repair site as well as improved recovery of key functional metrics, including ROM and maximal dorsiflexion. Further, these hydrogels were safe and did not impair tendon strength nor healing compared to the current standard of care. These dynamic, biocompatible hydrogels present a novel solution to the significant problem of peritendinous adhesions with clear translational potential.

  View details for DOI 10.1101/2025.02.22.639655

  View details for PubMedID 40060618

• Custom-engineered hydrogels for delivery of human iPSC-derived neurons into the injured cervical spinal cord. Biomaterials Doulames, V. M., Marquardt, L. M., Hefferon, M. E., Baugh, N. J., Suhar, R. A., Wang, A. T., Dubbin, K. R., Weimann, J. M., Palmer, T. D., Plant, G. W., Heilshorn, S. C. 2023; 305: 122400

  Abstract

  Cervical damage is the most prevalent type of spinal cord injury clinically, although few preclinical research studies focus on this anatomical region of injury. Here we present a combinatorial therapy composed of a custom-engineered, injectable hydrogel and human induced pluripotent stem cell (iPSC)-derived deep cortical neurons. The biomimetic hydrogel has a modular design that includes a protein-engineered component to allow customization of the cell-adhesive peptide sequence and a synthetic polymer component to allow customization of the gel mechanical properties. In vitro studies with encapsulated iPSC-neurons were used to select a bespoke hydrogel formulation that maintains cell viability and promotes neurite extension. Following injection into the injured cervical spinal cord in a rat contusion model, the hydrogel biodegraded over six weeks without causing any adverse reaction. Compared to cell delivery using saline, the hydrogel significantly improved the reproducibility of cell transplantation and integration into the host tissue. Across three metrics of animal behavior, this combinatorial therapy significantly improved sensorimotor function by six weeks post transplantation. Taken together, these findings demonstrate that design of a combinatorial therapy that includes a gel customized for a specific fate-restricted cell type can induce regeneration in the injured cervical spinal cord.

  View details for DOI 10.1016/j.biomaterials.2023.122400

  View details for PubMedID 38134472

• Hyaluronan and elastin-like protein (HELP) gels significantly improve microsphere retention in the myocardium. Biomaterials science Suhar, R. A., Doulames, V. M., Liu, Y., Hefferon, M. E., Figueroa, O. 3., Buabbas, H., Heilshorn, S. C. 2022

  Abstract

  Heart disease is the leading cause of death globally, and delivery of therapeutic cargo (e.g., particles loaded with proteins, drugs, or genes and cells) through direct injection into the myocardium is a promising clinical intervention. However, retention of deliverables to the contracting myocardium is low, with as much as 60-90% of payload being lost within 24 hr. Commercially-available injectable hydrogels, including Matrigel, have been hypothesized to increase payload retention but have not yielded significant improvements in quantified analyses. Here, we assess a recombinant hydrogel composed of chemically modified hyaluronan and elastin-like protein (HELP) as an alternative injectable carrier to increase cargo retention. HELP is crosslinked using dynamic covalent bonds, and tuning the hyaluronan chemistry significantly alters hydrogel mechanical properties including stiffness, stress relaxation rate, and ease of injectability through a needle or catheter. These materials can be injected even after complete crosslinking, extending the time window for surgical delivery. We show that HELP gels significantly improve in vivo retention of microsphere cargo compared to Matrigel, both 1 day and 7 days post-injection directly into the rat myocardium. These data suggest that HELP gels may assist with the clinical translation of therapeutic cargo designed for delivery into the contracting myocardium by preventing acute cargo loss.

  View details for DOI 10.1039/d1bm01890f

  View details for PubMedID 35411353

• Elastin-like Proteins to Support Peripheral Nerve Regeneration in Guidance Conduits. ACS biomaterials science & engineering Suhar, R. A., Marquardt, L. M., Song, S., Buabbas, H., Doulames, V. M., Johansson, P. K., Klett, K. C., Dewi, R. E., Enejder, A. M., Plant, G. W., George, P. M., Heilshorn, S. C. 2021; 7 (9): 4209-4220

  Abstract

  Synthetic nerve guidance conduits (NGCs) offer an alternative to harvested nerve grafts for treating peripheral nerve injury (PNI). NGCs have been made from both naturally derived and synthesized materials. While naturally derived materials typically have an increased capacity for bioactivity, synthesized materials have better material control, including tunability and reproducibility. Protein engineering is an alternative strategy that can bridge the benefits of these two classes of materials by designing cell-responsive materials that are also systematically tunable and consistent. Here, we tested a recombinantly derived elastin-like protein (ELP) hydrogel as an intraluminal filler in a rat sciatic nerve injury model. We demonstrated that ELPs enhance the probability of forming a tissue bridge between the proximal and distal nerve stumps compared to an empty silicone conduit across the length of a 10 mm nerve gap. These tissue bridges have evidence of myelinated axons, and electrophysiology demonstrated that regenerated axons innervated distal muscle groups. Animals implanted with an ELP-filled conduit had statistically higher functional control at 6 weeks than those that had received an empty silicone conduit, as evaluated by the sciatic functional index. Taken together, our data support the conclusion that ELPs support peripheral nerve regeneration in acute complete transection injuries when used as an intraluminal filler. These results support the further study of protein engineered recombinant ELP hydrogels as a reproducible, off-the-shelf alternative for regeneration of peripheral nerves.

  View details for DOI 10.1021/acsbiomaterials.0c01053

  View details for PubMedID 34510904

• Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy. Science advances Marquardt, L. M., Doulames, V. M., Wang, A. T., Dubbin, K., Suhar, R. A., Kratochvil, M. J., Medress, Z. A., Plant, G. W., Heilshorn, S. C. 2020; 6 (14): eaaz1039

  Abstract

  Transplantation of patient-derived Schwann cells is a promising regenerative medicine therapy for spinal cord injuries; however, therapeutic efficacy is compromised by inefficient cell delivery. We present a materials-based strategy that addresses three common causes of transplanted cell death: (i) membrane damage during injection, (ii) cell leakage from the injection site, and (iii) apoptosis due to loss of endogenous matrix. Using protein engineering and peptide-based assembly, we designed injectable hydrogels with modular cell-adhesive and mechanical properties. In a cervical contusion model, our hydrogel matrix resulted in a greater than 700% improvement in successful Schwann cell transplantation. The combination therapy of cells and gel significantly improved the spatial distribution of transplanted cells within the endogenous tissue. A reduction in cystic cavitation and neuronal loss were also observed with substantial increases in forelimb strength and coordination. Using an injectable hydrogel matrix, therefore, can markedly improve the outcomes of cellular transplantation therapies.

  View details for DOI 10.1126/sciadv.aaz1039

  View details for PubMedID 32270042

• Human iPSC-Derived Corticospinal Neuronal Grafts To Repair Cervical Spinal Cord Injury Doulames, V., Weimann, J., Plant, G. W. SAGE PUBLICATIONS INC. 2019: 492

  View details for Web of Science ID 000476672400073

• Stem cell therapies for acute spinal cord injury in humans: a review NEUROSURGICAL FOCUS Jin, M. C., Medress, Z. A., Azad, T. D., Doulames, V. M., Veeravagu, A. 2019; 46 (3): E10

  Abstract

  Recent advances in stem cell biology present significant opportunities to advance clinical applications of stem cell-based therapies for spinal cord injury (SCI). In this review, the authors critically analyze the basic science and translational evidence that supports the use of various stem cell sources, including induced pluripotent stem cells, oligodendrocyte precursor cells, and mesenchymal stem cells. They subsequently explore recent advances in stem cell biology and discuss ongoing clinical translation efforts, including combinatorial strategies utilizing scaffolds, biogels, and growth factors to augment stem cell survival, function, and engraftment. Finally, the authors discuss the evolution of stem cell therapies for SCI by providing an overview of completed (n = 18) and ongoing (n = 9) clinical trials.

  View details for DOI 10.3171/2018.12.FOCUS18602

  View details for Web of Science ID 000460130200010

  View details for PubMedID 30835679

• Induced Pluripotent Stem Cell Therapies for Cervical Spinal Cord Injury. International journal of molecular sciences Doulames, V. M., Plant, G. W. 2016; 17 (4)

  Abstract

  Cervical-level injuries account for the majority of presented spinal cord injuries (SCIs) to date. Despite the increase in survival rates due to emergency medicine improvements, overall quality of life remains poor, with patients facing variable deficits in respiratory and motor function. Therapies aiming to ameliorate symptoms and restore function, even partially, are urgently needed. Current therapeutic avenues in SCI seek to increase regenerative capacities through trophic and immunomodulatory factors, provide scaffolding to bridge the lesion site and promote regeneration of native axons, and to replace SCI-lost neurons and glia via intraspinal transplantation. Induced pluripotent stem cells (iPSCs) are a clinically viable means to accomplish this; they have no major ethical barriers, sources can be patient-matched and collected using non-invasive methods. In addition, the patient's own cells can be used to establish a starter population capable of producing multiple cell types. To date, there is only a limited pool of research examining iPSC-derived transplants in SCI-even less research that is specific to cervical injury. The purpose of the review herein is to explore both preclinical and clinical recent advances in iPSC therapies with a detailed focus on cervical spinal cord injury.

  View details for DOI 10.3390/ijms17040530

  View details for PubMedID 27070598

  View details for PubMedCentralID PMC4848986

• Social interaction attenuates the extent of secondary neuronal damage following closed head injury in mice FRONTIERS IN BEHAVIORAL NEUROSCIENCE Doulames, V. M., Vilcans, M., Lee, S., Shea, T. B. 2015; 9: 369

  Abstract

  Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window (termed retrieval + extinction) attenuates fear responding and prevents the return of fear in Pavlovian fear conditioning (Monfils et al., 2009). To date, the mechanisms that explain the different behavioral outcomes between standard extinction and retrieval + extinction remain poorly understood. Here we sought to examine the differential temporal engagement of specific neural systems by these two approaches using Arc catFISH (cellular compartment analysis of temporal activity using fluorescence in situ hybridization (FISH)). Our results demonstrate that extinction and retrieval + extinction lead to differential patterns of expression, suggesting that they engage different networks. These findings provide insight into the neural mechanisms that allow extinction during reconsolidation to prevent the return of fear in rodents.

  View details for DOI 10.3389/fnbeh.2015.00275

  View details for Web of Science ID 000362837700001

  View details for PubMedID 26834596

  View details for PubMedCentralID PMC4722140

• Environmental enrichment and social interaction improve cognitive function and decrease reactive oxidative species in normal adult mice INTERNATIONAL JOURNAL OF NEUROSCIENCE Doulames, V., Lee, S., Shea, T. B. 2014; 124 (5): 369-376

  Abstract

  Environmental stimulation and increased social interactions stimulate cognitive performance, while decrease in these parameters can exacerbate cognitive decline as a function of illness, injury, or age. We examined the impact of environmental stimulation and social interactions on cognitive performance in healthy adult C57B1/6J mice. Mice were housed for 1 month individually or in groups of three (to prevent or allow social interaction) in either a standard environment (SE) or an enlarged cage containing nesting material and items classically utilized to stimulate exploration and activity ("enriched environment"; EE). Cognitive performance was tested by Y maze navigation and Novel Object Recognition (NOR; which compares the relative amount of time mice spent investigating a novel vs. a familiar object). Mice maintained for 1 month under isolated conditions in the SE statistically declined in performance versus baseline in the Y maze (p < 0.02; ANOVA). Performance under all other conditions did not change from baseline. Maintenance in groups in the SE statistically improved NOR (p < 0.01), whereas maintenance in isolation in the SE did not alter performance from baseline. Maintenance in the EE statistically improved performance in NOR for mice housed in groups and individually (p < 0.01). Maintenance under isolated conditions slightly increased reactive oxygen/nitrogen species (ROS/RNS) in brain. Environmental enrichment did not influence ROS/RNS. These findings indicate that environmental and social enrichment can positively influence cognitive performance in healthy adult mice, and support the notion that proactive approaches may delay age-related cognitive decline.

  View details for DOI 10.3109/00207454.2013.848441

  View details for Web of Science ID 000334403300008

  View details for PubMedID 24102158

• Synergistic effects of dopamine D2-like receptor antagonist sulpiride and beta-blocker propranolol on learning in the Carousel maze, a dry-land spatial navigation task PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR Prokopova, I., Bahnik, S., Doulames, V., Vales, K., Petrasek, T., Svoboda, J., Stuchlik, A. 2012; 102 (1): 151-156

  Abstract

  Spatial navigation attracts the attention of neuroscientists as an animal analogue of human declarative memory. The Carousel maze is a dry-land navigational paradigm, which proved to be useful in studying neurobiological substrates of learning. The task involves avoidance of a stable sector on a rotating arena and is highly dependent upon the hippocampus. The present study aims at testing hypothesis that sulpiride (a centrally-active dopamine D2-like receptor antagonist) and propranolol (a beta-blocker) impair spatial learning in the Carousel maze after combined systemic administration. These doses were previously shown to be subthreshold in this task. Results showed that both substances affected behavior and significantly potentiated their negative effects on spatial learning. This suggests central interaction of both types of receptors in influencing acquisition of this dynamic-environment task.

  View details for DOI 10.1016/j.pbb.2012.04.003

  View details for Web of Science ID 000305200600023

  View details for PubMedID 22525744

• Environmental Enrichment can Prevent Cognitive Decline Induced by Dietary Oxidative Challenge JOURNAL OF ALZHEIMERS DISEASE Lee, S., Doulames, V., Donnelly, M., Levasseaur, J., Shea, T. B. 2012; 28 (3): 497-501

  Abstract

  Alzheimer's disease encompasses multiple risk factors; convergence may be necessary for clinical manifestation. Mice received a complete diet or one lacking folate and vitamin E and containing iron as a pro-oxidant, in a standard environment (SE) or a large cage containing objects to stimulate exploration/activity (enriched environment; EE). Mice declined in maze navigation on the deficient versus complete diet in the SE but not the EE. Mice on the complete diet demonstrated superior performance in the EE versus SE. The EE reduced brain lipid and protein oxidation. These findings suggest that maintaining nutrition and activity may delay age-related cognitive decline.

  View details for DOI 10.3233/JAD-2011-111562

  View details for Web of Science ID 000300414500001

  View details for PubMedID 22045493

• Combined administration of alpha1-adrenoceptor antagonist prazosin and beta-blocker propranolol impairs spatial avoidance learning on a dry arena BEHAVIOURAL BRAIN RESEARCH Petrasek, T., Doulames, V., Prokopova, I., Vales, K., Stuchlik, A. 2010; 208 (2): 402-407

  Abstract

  Spatial learning is a widely studied type of animal behavior often considered as a model of higher human cognitive functions. Noradrenergic receptors play a modulatory role in many nerve functions, including vigilance, attention, reward, learning and memory. The present study aimed at studying the effects of separate or combined systemic administration of the alpha1-adrenergic antagonist prazosin (1 and 2 mg/kg) and beta-blocker propranolol (5 and 20 mg/kg) on the hippocampus-dependent learning in the active allothetic place avoidance (AAPA) task. Both centrally active drugs impaired spatial learning when administered together, exerting no effect in separate applications. Locomotion was impaired only in a combined application of higher doses of both drugs (2 mg/kg prazosin and 20 mg/kg propranolol). These results suggest an in vivo interaction between these two types of receptors in spatial navigation regulation.

  View details for DOI 10.1016/j.bbr.2009.12.025

  View details for Web of Science ID 000276621200013

  View details for PubMedID 20035798