Biomedical Engineering Reference
In-Depth Information
replaced with a stainless steel electrode. This is lowered to the depth of the carbon
fi ber microelectrode during the experiment (using an identical micromanipula-
tor), and the lesion is made by passing current (100
A, 5 s) through it. It is
possible to make several lesions in a single animal to demonstrate electrode
placement from multiple experiments. During histological preparation, slices are
stained with potassium ferricyanide (in addition to thionin) to aid visualization
of the electrode-induced lesion.
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5. Applications
5.1. Intracranial Self-Stimulation
Intracranial self-stimulation is a behavioral paradigm whereby subjects carry
out an operant task to receive direct electrical stimulation of specifi c regions
of their brains
(19)
. Stimulation of the regions including the mesencephalic
dopaminergic cell bodies or of the lateral hypothalamus that includes the
ascending dopaminergic pathways are both reinforcing in this paradigm. It
is believed that dopamine is involved in the reinforcing properties of this
behavior, as it can be abolished by selective lesion of dopaminergic neurons
(20)
. To investigate further the role of dopamine, fast-scan cyclic voltammetry
was used to monitor dopamine in terminal regions during intracranial self-
stimulation of the ventral tegmental area/substantia nigra.
Rats were allowed free access to a lever, depression of which caused an
electrical stimulation (24 pulses, 60 Hz, ~120
A) to be applied across the
stimulating electrode on a fi xed-ratio 1 schedule. Within 1 d, rats usually
learned to freely lever-press for intracranial self-stimulation. Dopamine was
monitored using fast-scan cyclic voltammetry throughout the training and
test sessions.
In animals in which the stimulating electrode was positioned such that
stimulation produced detectable dopamine release, intracranial self-stimulation
behavior was acquired. However, in those in which the stimulating electrode
did not evoke dopamine release, the animals did not acquire the behavior,
suggesting that activation of dopaminergic neurons is required for intracranial
self-stimulation to be reinforcing.
In animals that did acquire intracranial self-stimulation behavior, the nor-
mally robust evoked dopamine signals disappeared as the animal acquired the
lever-pressing for intracranial self-stimulation. This attenuation occurred
despite the fact that experimenter-delivered electrical stimulation evoked
dopamine release prior to the intracranial self-stimulation session. Furthermore,
detectable dopamine release could be evoked, once again, by experimenter-
delivered stimulations at the end of the session. Finally, if a lever-press record
during an intracranial self-stimulation session from one animal was “played
back” to another animal, as a yoked control, dopamine release could be detected
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