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Basic Principles of Neurology

3 important questions on Basic Principles of Neurology

What will be the consequences of activation of the GABAA receptors for the Clflux across the membrane? Will there be an influx or an efflux for Cl- ? Explain your answer

As mentioned in the text, GABA is an inhibitory neurotransmitter, thus it leads to hyperpolarization of the cells. Since the GABAA receptor is coupled to Cl- , an anion, it can be assumed that Cl flows into the cell. (see also the answer to question 8).

When benzodiazepines are given for prolonged periods of time, tolerance usually develops. This means that its effect diminishes over time. Basically, tolerance can result from two different mechanisms: metabolic tolerance (because the drug is more quickly metabolized) or cellular tolerance (because the number of receptors is reduced). What simple animal experiment can be done to determine whether a benzodiazepine like diazepam induce metabolic or cellular tolerance?

There is actually more than one answer to this one . For instance you could measure the concentration of the benzodiazepines and see if the metabolism has changed. Alternatively you could give GABA or a direct GABA agonist that is not metabolized by the same enzymes as benzosdiazepines. If the effect is reduced, then the number of receptors must be reduced (cellular tolerance). If the effect is not reduced, then the reduced effects of benzodiazepines must be due to metabolic tolerance. Ideally you would like to do both, since some drugs can induce cellular AND metabolic tolerance.

Does the reverse also hold true? In other words do peripherally acting drugs always have central side effects too? Explain your answer.

No. Since the brain is protected by the blood brain barrier it is often, though not always, possible to design drugs that have a peripheral effect but do not cross the blood brain barrier.