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Optogenetics Behavioural Experiments place preference in neurobiology of

addictive diseases

Optogenetics is a biological technique which involves the use of light to


control cells in living tissue, typically neurons, that have been genetically
modified to express light-sensitive ion channels. It is
a neuromodulation method employed in neuroscience that uses a
combination of techniques from optics and genetics to control and monitor
the activities of individual neurons in living tissueeven within freely-moving
animalsand to precisely measure the effects of those manipulations in realtime.[1] The key reagents used in optogenetics are light-sensitive
proteins. These proteins can readily be introduced into target cells by
various techniques, allowing scientists to rapidly and accurately turn
individual neurons on and off without the need for additional drugs or
chemicals, thus this is a refined research method to be used nowadays.
The place preference behavioral test pursues an interest in circuits that
mediate drug taking behavior and it uses rats as subjects. The test chamber
is divided into two halves that are distinguished visually through different
patterns and the animal only receives stimulation in one of the two
chambers. If a circuit is reinforcing, the animal will prefer to spend most of its
time in the chamber in which it receives the stimulation (conversely, if the
circuit is aversive, it will spend most of its times in the opposite chamber).If a
circuit reinforces behavior (activation of the circuit promotes subsequent,
repeated activation), this is an approximation of reward or the sense of
pleasure that the animal perceives through taking a drug.
Another type of experiment used to determine the behavior of drug taking is
the one used in the research conducted by Billy T. Chen in the NIDA
Intramural Research Program, Decreased Excitability of Prelimbic Pyramidal
Neurons Induced by Extended Cocaine Self-Administration Contributes To
Compulsive Drug Seeking. Research shows that different brain regions are
involved in an individuals transition to drug abuse. As the ability of neurons
to compensate for injury and disease fluctuates within these regions, drug
seeking behaviors can become more compulsive. Previous studies suggest
that compulsive drug-seeking may result from inadequate functioning of the
decision-making centers in the prefrontal cortex.

To test this hypothesis, Dr. Chen and his research team trained adult male
rats to self-administer cocaine on a seek-take chain schedule for about 2
months. After this period, they were exposed to foot shock punishment
during self-administration. Researchers observed both a shock-resistant
group (continued to self-administer despite shocks) and a shock-sensitive
group (suspended all cocaine-seeking when shocked) before performing ex
vivo studies of deep-layer pyramidal neurons in the prelimbic area. Results
showed that neurons in the prelimbic area of cocaine-experienced rats
showed significant decreases in membrane excitability compared to cocainenave rats. Furthermore, this effect was more pronounced in shock-resistant
rats than in shock-sensitive rats.
The research team also used in vivo optogenetic stimulation to rescue
cocaine-induced hypoactivity in the prelimbic area in the shock-resistant
rats. Dr. Chens findings showed that prolonged cocaine self-administration
decreased excitability in prelimbic neurons, which may contribute to
compulsive cocaine-seeking behaviors.
I would conduct this kind of experiments using other drugs of abuse, such as
heroin, methamphetamines, and opioids in order to understand the circuits
that mediate those drugs taking behavior.
In the first place, the research team would need three rats, one for each
drug. The procedure of optogenetics could be permanently altering the
behaviour of animals, so the number of subjects that are used is reduced.
However, the optogenetics technique is not known to induce pain to animal
subjects.

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