Wednesday, April 27, 2016

Introduction to Psychobiology - Part 5 (Drug Effects)






For more information about psychobiology, please check out: "Physiology of Behavior," by Neil Carlson


We mentioned before that drug effects are the biological and behavioral outcomes produced by introducing drugs into the body. Now we will introduce a concept known as drug-response curve that will connect to past material. This is refers to a graph that displays up to which point there is an the maximum effect obtained (1). In the picture on the right we can observe that the blue line represents the desired effect, in this case the analgesic effect, of morphine. Meanwhile, the red line describes when the dose of a drug produces a negative outcome, in this case the depressive effect. To measure when a drug is safe, we utilize (there are other methods to measure safety) the therapeutic index. This is the ratio between two numbers. The first one is the amount of a dose needed in order for 50% of a sample to obtain the desired effect of a drug, the second number is obtained by calculating the dose needed to cause 50% of a sample to die. The lower the ratio, the more dangerous it is to make a mistake by prescribing a drug (2).


There are two reasons why the effects of drugs vary:
  1. Each drug has different sites of action
  2. The affinity, which is the readiness by which two molecules attach, of a drug.

Binding Sites for Drugs

There are two types of binding sites. Direct and Indirect. In the former, the binding site is competitive. This means that neurotransmitters and drugs compete for the same binding site. In the latter, neurotransmitters and drugs have a separate one.




If you looked at the pictured above, you might have noticed that there are also two extra categories: agonist and an antagonist. Antagonists help inhibit the effects of the natural ligand and an agonist facilitates the effect of a neurotransmitter (3).



Interesting Fact: There are two possible outcomes for repeated use of drugs. Tolerance, which means that the effectiveness of a drugs diminishes, or sensitization, which means that the effectiveness increases.

Turnover Model

There are several ways a drug can effect neural activity, we will only cover seven (2).

  1. Synthesis: A drug can inactivate the synthesis of a neurotransmitter
  2. Storage: A drug can prevent the storage of a neurotransmitter (NT) in vesicles.
  3. Release: A drug can stimulate the release of a NT
  4. Receptor Activation: A drug can help stimulate receptors. There are two: postsynaptic and presynaptic. We will cover the latter later.
  5. Enzymatic Deactivation: A drug can help the enzymes get rid of a NT
  6. Reuptake: A drug can inhibit reuptake.
Like promised let us cover presynaptic heteroreceptors. This are usually found in axoaxonic synapses. The second axon is sensitive to the NTs of the first one. Thus, if there is presynaptic inhibition the calcium channels will close and there will be less or none NTs released from the second axon. If the opposite happens, presynaptic facilitation, the calcium channels will open, thus, facilitating NTs release. Remember that calcium is required for exocytosis. This is when a vesicle becomes part of the membrane (4).



References

1. https://science.education.nih.gov/supplements/nih2/chemicals/guide/pdfs/lesson3.pdf

2. "Physiology of Behavior," by Neil Carson

3. http://biowiki.ucdavis.edu/Core/Biochemistry/Transport_and_Kinetics/Enzyme_Inhibition/Agonist_and_Antagonist_of_Ligand_Binding

4. http://academic.brooklyn.cuny.edu/biology/bio4fv/page/exocy.htm