Development of an MK-801 Hyperactivity Model in Zebrafish Larvae - Analysis of Locomotor Activity and Brain Neurotransmitters
(2014) MOBM11 20132Degree Projects in Molecular Biology
- Abstract
- Popular science summary:
An MK-801 Hyperactivity Model in Zebrafish Larvae
Schizophrenia is a mental disorder characterized by psychosis, depression and cognitive impairments. The severity of this disease is easily underestimated, since the manifestations are not consequently lethal. Additionally, Schizophrenia is correlated with a 50 times increased risk of attempted suicide. Considering that approximately 1 % of the population has this disease raises concerns about the fact that a cure is yet to be found. One of the most important tools in the development of new drugs for mental disorders is animal models. This is because the symptoms typically manifesting these disorders are difficult to evaluate by other methods. The... (More) - Popular science summary:
An MK-801 Hyperactivity Model in Zebrafish Larvae
Schizophrenia is a mental disorder characterized by psychosis, depression and cognitive impairments. The severity of this disease is easily underestimated, since the manifestations are not consequently lethal. Additionally, Schizophrenia is correlated with a 50 times increased risk of attempted suicide. Considering that approximately 1 % of the population has this disease raises concerns about the fact that a cure is yet to be found. One of the most important tools in the development of new drugs for mental disorders is animal models. This is because the symptoms typically manifesting these disorders are difficult to evaluate by other methods. The psychosis-inducing compound MK 801 has previously been used in rodent models to induce a schizophrenia-like state. Unfortunately, the available models today lack both sufficient throughput and cost-efficiency which makes it increasingly more difficult to perform compound evaluations on a larger scale.
Zebrafish as a Model Organism
The use of zebrafish larvae in disease models is a new approach that might help alleviate some of these issues. Zebrafish have the benefit of a small size, high reproduction rate, low costs for care and husbandry and high similarity to humans regarding the central nervous system. In this work, attempts were made to establish an MK 801 hyperactivity model, assessing several aspects of the larvae behavior in response to drug compounds. Hopefully, this model could be used to discover new antipsychotic drugs. Furthermore, a procedure for dissecting larvae brains, with subsequent analysis of brain neurotransmitters relevant to schizophrenia, was developed. To my knowledge, this has not been done before and might be an important tool in establishing drug models.
It was here found that treatment with MK 801 only modestly increased larvae activity, and only for a dose much lower than what has been suggested in recently published articles. Additionally, a similarly low dose was found to increase the amounts of brain neurotransmitters relevant to Schizophrenia. This suggests that the dose might need to be re-evaluated. Furthermore, the effects on brain neurotransmitters were only seen if the larvae had been treated continuously, with low doses of MK 801, for one week prior to administration of the acute dose. It is possible that a “sub chronic” model, where treatment is given over a longer period of time, is a well suited approach when establishing an MK 801 model.
Supervisor: Fredrik Ek
Master’s Degree Project in Pharmacology 30 Credits Fall 2013
Department of Experimental Medical Science, Lund University (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/4456473
- author
- Jönsson, Daniel
- supervisor
-
- Fredrik Ek LU
- organization
- course
- MOBM11 20132
- year
- 2014
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 4456473
- date added to LUP
- 2014-06-02 15:55:22
- date last changed
- 2014-06-02 15:55:22
@misc{4456473,
abstract = {{Popular science summary:
An MK-801 Hyperactivity Model in Zebrafish Larvae
Schizophrenia is a mental disorder characterized by psychosis, depression and cognitive impairments. The severity of this disease is easily underestimated, since the manifestations are not consequently lethal. Additionally, Schizophrenia is correlated with a 50 times increased risk of attempted suicide. Considering that approximately 1 % of the population has this disease raises concerns about the fact that a cure is yet to be found. One of the most important tools in the development of new drugs for mental disorders is animal models. This is because the symptoms typically manifesting these disorders are difficult to evaluate by other methods. The psychosis-inducing compound MK 801 has previously been used in rodent models to induce a schizophrenia-like state. Unfortunately, the available models today lack both sufficient throughput and cost-efficiency which makes it increasingly more difficult to perform compound evaluations on a larger scale.
Zebrafish as a Model Organism
The use of zebrafish larvae in disease models is a new approach that might help alleviate some of these issues. Zebrafish have the benefit of a small size, high reproduction rate, low costs for care and husbandry and high similarity to humans regarding the central nervous system. In this work, attempts were made to establish an MK 801 hyperactivity model, assessing several aspects of the larvae behavior in response to drug compounds. Hopefully, this model could be used to discover new antipsychotic drugs. Furthermore, a procedure for dissecting larvae brains, with subsequent analysis of brain neurotransmitters relevant to schizophrenia, was developed. To my knowledge, this has not been done before and might be an important tool in establishing drug models.
It was here found that treatment with MK 801 only modestly increased larvae activity, and only for a dose much lower than what has been suggested in recently published articles. Additionally, a similarly low dose was found to increase the amounts of brain neurotransmitters relevant to Schizophrenia. This suggests that the dose might need to be re-evaluated. Furthermore, the effects on brain neurotransmitters were only seen if the larvae had been treated continuously, with low doses of MK 801, for one week prior to administration of the acute dose. It is possible that a “sub chronic” model, where treatment is given over a longer period of time, is a well suited approach when establishing an MK 801 model.
Supervisor: Fredrik Ek
Master’s Degree Project in Pharmacology 30 Credits Fall 2013
Department of Experimental Medical Science, Lund University}},
author = {{Jönsson, Daniel}},
language = {{eng}},
note = {{Student Paper}},
title = {{Development of an MK-801 Hyperactivity Model in Zebrafish Larvae - Analysis of Locomotor Activity and Brain Neurotransmitters}},
year = {{2014}},
}