3 - 8 - 29. Nicotine Addiction at Circuit and Cellular Level- Upregulation via “Inside-Out” Mechanis

3 - 8 - 29. Nicotine Addiction at Circuit and Cellular Level- Upregulation via “Inside-Out” Mechanis

Info icon This preview shows pages 1–3. Sign up to view the full content.

View Full Document Right Arrow Icon
Hello. Most of the slides in this mini-lecture come from research seminars that I have given recently, or plan to give. The topic. Is still changes in the brain with chronic nicotine. Curiously enough, in 1983 it was first noticed that in an animal given chronic nicotine, maintained or repeated for a week or two, there were more nicotenic receptors. That is, they were up regulated. This is curious because most of us would have thought that during drug addiction, a component of tolerance would be actual decreases in receptors. How this played out and what causes it I will tell you in this lecture. So we are still trying to go all the way from genes to behavior, or from behavior back to genes. And as stated, chronic nicotine increases the number of nicotinic receptors. These are functional nicotinic receptors. But, interestingly enough, this so-called up regulation actually displays remarkable selectivity at every level that has been thus far examined. So this selectivity occurs only in some brain regions, only in some cell types, Dopamine cell types, versus cell types that make GABA or those that make glutamate. The up regulation occurs only in some settled, sub cellular compartments. Axon terminals versus somatodendritic. And only some sub-types of nicotinic receptors are up regulated, mostly high sensitivity to nicotine rather than low sensitivity to nicotine. And furthermore, there may, even be a dependence on the detail stoichiometry of the nicotinic receptors, so let's follow this story. This is a, quick summary, which you do not need to remember in any way for quizs or exams, here is, are diagrams of key regions of the brain, the, VTA and striatum. The medial habenula, which we've heard in the previous talk. And the hippocampus, which we've heard about in a previous talks. This table basically tells us where after we've given chronic nicotine for a week or two. Cells grow new nicotinic receptors. In some cells there is, are no new nicotinic receptors at all. In others there are new nicotinic receptors on t he terminals projecting to another area but not on the cell body. In others, there are nicotinic receptors both on the cell body and on the terminals. Now one point to be made is that as you can see up regulation is quite robust on gabaergic cells. These are cells that usually inhibit other cells. And so the paradox that I stated, how could up regulation? Be associated with tolerance involves a change in the sign, it involves the fact that we have nicotinic receptors
Image of page 1

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
up regulated. But they are in, inhibitory neurons. Not on excitatory neurons. Let's go on, now, and talk about another aspect of up regulation. And this is the connection with desensitization. You'll remember that when we learned about nicotinic receptors, we learned that they can be activated. And then they can become desensitized. And I told you that there's presently a very detailed discussion about which action of nicotine causes activation, and which causes desensitization. Either activation or
Image of page 2
Image of page 3
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern