Pre-clinical trial – the stage in which medications or therapies are tested on
animal models – is a crucial part of drug development. This makes it possible
for scientists to assess the therapeutic benefit and any side effects before the
drug is administered to patients.
Prof. Ilan Golani from Tel Aviv
University’s zoology department and the Sagol School for Neuroscience notes that
because of their relative genetic similarity to humans, mice are most commonly
used as lab animals.
Countless hours and billions of dollars have been
spent on developing mouse models whose genetics can be engineered to mimic human
diseases and disorders.
And while many of these models have made an
invaluable contribution to the advancement of research, such as models for
Parkinson’s disease and cancers, others have proven less
effective.
Golani and his fellow researchers – Prof. Yoav Benjamini from
the statistics and operations research department at the Sagol School of
Neuroscience and Dr. Ehud Fonio from the Weizmann Institute – are contesting the
viability of the models used for chronic disorders, such as the common
generalized anxiety disorder (GAD). Using a hundred-fold longer experimental
time-frame and comparing against wild mice, the researchers have found that the
lab mice used to model chronic anxiety do not actually experience the
disorder.
Instead, the behavior measured by scientists in the first
minutes of an experiment is a transient response to the novel environment. With
time, the mice revert back to their true temperament – calm for lab mice and
anxiety for wild mice. This discovery, which has been reported in the journals
PLoS One and Nature Methods, could explain why most candidate drugs developed
using this mouse model have poor therapeutic value when applied to human chronic
diseases, including GAD and other brain disorders, Golani says, noting that this
is a well-recognized problem in the field.
A chronically anxious mouse
model is crucial for testing anti-anxiety therapies, says Golani. Currently,
scientists use a specific strain of lab mice thought to be particularly anxious.
During experiments, they are set down into a unique environment and monitored
for signs of anxiety, such as spending time in sheltered rather than exposed
spaces. Once new therapies are administered, the mice are observed for a
reduction in anxious behaviors.
The researchers compared the lab mouse
strain used for GAD testing to a strain of first-generation wild mice born into
captivity. The time frame of the experiment was extended from a few minutes
through to 45 hours.
Though the lab mice appeared more anxious at first,
the researchers surprisingly discovered that the lab mice settle into calm
behavior while the wild mice settle into anxious behavior: “In nature, mice must
always be on high alert or they will get preyed upon,” explains
Golani.
In another article, the researchers call for similar scrutiny of
other behavioral animal models. Should each experiment be conducted in many
laboratories? It’s not necessary, Benjamini concludes.
“Developing a
collaborative database that draws on the different experiments conducted across
the globe, as well as appropriate data mining tools, can yield for the scientist
in her isolated lab the needed yardstick to check for the replicability of her
findings.
The community-based effort will help researchers screen their
useful findings from questionable ones.
Going under, smiling
Children who
watch a video immediately before undergoing surgery have less anxiety during
inhaled anesthesia induction, the most stressful time for children throughout
the peri-operative process.
Up to half of children display significant distress
at the point of inhaled induction and separation from parents. Fear or exposure
to a foreign environment may cause children to display high levels of distress
during this time.
As a result, those who experience high levels of distress at
anesthesia induction may have more pain during recovery, The research study was
conducted by student Katerine Mifflin of Dalhousie University in Halifax, Nova
Scotia, under the supervision of Profs. Jill Chorney and Thomas
Hackman.
“Our study is one of the first to examine the effectiveness of
video to reduce anxiety in children undergoing inhaled induction,” says Chorney.
“On the basis of the previous research with cartoon and video use in minor
medical procedures, it was expected that playing a video clip during anesthesia
induction would be effective at reducing anxiety.”
“The 97 study
participants were assigned to either the experimental video distraction group or
control group,” says Chorney.
“Participants in the video distraction group were
presented with a list of age-appropriate videos to choose from, asked what they
enjoyed viewing at home and a similar clip was found on YouTube for the child to
view during induction. Enabling the participant to choose a video allowed for
parental approval of the video and gave the child the opportunity to become
familiar with the content, thus becoming engaged with the distractor and
possibly avoiding anticipatory anxiety.”
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