So
Shernaz Bamji, a Professor in the Department of Cellular and
Physiological Sciences, thought that extra cadherin in the reward
circuit would make their mice more prone to cocaine addiction. But she and her collaborators found the opposite to be true, as they explain in an article published today in
‘A genetically engineered mouse that does not become addicted to cocaine has been developed by researchers. This suggests that habitual drug use is more a matter of genetics and biochemistry than just poor judgment.’
Dr. Bamji and her collaborators injected cocaine into mice over a
number of days and immediately placed in a distinctly decorated
compartment in a three-room cage, so that they would associate the drug
with that compartment. After several days of receiving cocaine this way,
the mice were put into the cage and allowed to spend time in any
compartments they preferred.
The normal mice almost always gravitated to
the cocaine-associated compartment, while the mice with extra cadherin
spent half as much time there - indicating that these mice hadn't formed
strong memories of the drug.
To understand that unexpected result, Dr. Bamji and her associates
in UBC's Life Sciences Institute analyzed the brain tissue of the
genetically engineered mice.
They found that extra cadherin prevents a type of neurochemical
receptor from migrating from the cell's interior to the synaptic
membrane. Without that receptor in place, it's difficult for a neuron to
receive a signal from adjoining neurons. So the synapses don't
strengthen and the pleasurable memory does not "stick."
"Through genetic engineering, we hard-wired in place the synapses
in the reward circuits of these mice," says graduate student Andrea
Globa, a co-lead author with former graduate student Fergil Mills. "By
preventing the synapses from strengthening, we prevented the mutant mice
from 'learning' the memory of cocaine, and thus prevented them from
becoming addicted."
Their finding provides an explanation for previous studies showing
that people with substance use problems tend to have more genetic
mutations associated with cadherin and cell adhesion. As studies such as
this one illuminate the biochemical underpinnings of addiction, it
could lead to greater confidence in predicting who is more vulnerable to
drug abuse - and enable people to act on that knowledge.
Unfortunately, finding a way of augmenting cadherin as a way of
resisting addiction in humans is fraught with pitfalls. In many cases,
it's important to strengthen synapses - even in the reward circuit of
the brain.
"For normal learning, we need to be able to both weaken and
strengthen synapses," Dr. Bamji says. "That plasticity allows for the
pruning of some neural pathways and the formation of others, enabling
the brain to adapt and to learn. Ideally, we would need to find a
molecule that blocks formation of a memory of a drug-induced high, while
not interfering with the ability to remember important things."
Source: Eurekalert
