Overactivity of the brain dopamine system originating in the ventral tegmental area (VTA) is thought
to play an important role in the neuropsychiatric disorder schizophrenia. Drugs used for treating
schizophrenia – so-called antipsychotic drugs (APD's) - interact with the VTA dopamine system. However,
dopamine neurons in other brain areas like e.g. the nigrostriatal system can also be affected by the APD's,
resulting is serious (Parkensonian-like) side effects. The reason for this is that the pharmacological
properties of dopamine neurons of the SN and VTA are quite similar. Looking for targets involved in
regulating the electrical activity of the dopamine neurons in these two brain areas can help to develop
new APD's that have less or no side effects.
Therefore we have developed a rat in vitro slice preparation
where the (differential) effects of drugs on the electrical activity of dopamine neurons in the SN and VTA
can be recorded. We investigate the mechanisms underlying the effects of drugs that may have potential APD
properties and/or are thought to play a role in schizophrenia. For example, serotonergic drugs can be
investigated that differentially modulate (auto)-inhibition (through dopamine D2 receptors or GABA-B receptors)
of the dopamine neurons in the SN and VTA, a process that is thought to be important for the mechanism of
action of a certain class of APD's.
You will learn to make slices from the midbrain of the rat. In these slices you will make extracellular
recordings of dopamine neurons in the substantia nigra and ventral tegmental area. In vitro these neurons
fire action potentials at a stable (pace-maker-like) rate and you will determine the effects of (new) drugs
on the electrical activity of these neurons.
The extracellular recording technique is a challenging technique to learn. Therefore a relatively long
training period a needed before reliable recordings can be made. However, once one has mastered this method,
it allows an in-depth analysis of (new) drugs at a functional level and can it provide important clues regarding
the mechanisms of action of these compounds.
Duration: 35 weeks (50 EC) - 42 weeks (60 EC)
Contact: Dr. T.R. Werkman
SILS-CNS, room C3 - 269
Science Park Amsterdam
Phone: 020-5257632
e-mail: t.r.werkman@uva.nl