BIONB 392 - Drugs and the Brain

Discussion Sections

Tuesday, 9:00-9:50am B104 Comstock	Tuesday, 12:20-1:10pm B106 Comstock	Tuesday, 1:25-2:15pm B106 Comstock	Tuesday, 2:30-3:20pm B106 Comstock	Tuesday, 3:35-4:25pm G37 Plant Science
Lily Abagyan Neha Bodapati Daniel Butterly Gracielle Cabungcal Jason Dietz Wing Kay Fok Kate Goldberg Jin Hao Stacey Lynch Julianna Marwell Rekha Reddy Amanda Ribbeck Bass Storch Dovie Watson	Jennifer Bakalar Adrienne Barasch Rachel Brandstadter Emily Gordon Elizabeth Howes Theodore Lee Maxwell Li Molly Marino Justin Musaffi Abhijit Pal Daniel Rodriguez Lorelei Stoica Jayan Zaman	Jonathan Berry Danielle Bolling Elizabeth Chamberlain Dana Cruite Dmitry Dvoskin Kate Justus Scott Leopold Nicholas Macpherson David Mak Vanessa Mondestin Steven Sachs Abigail Secovnie Mikhail Shub Divya Sood	Melanie Adamsky Sarah Birman Adam Bisogni Kelly Burke Patrick Chen Tara Kaushal Joshua Lubner Andrew Mcreynolds Kaitlyn Mitchell Alexandra Pritchett Bernard Tarr Jessica Vasquez	Aneesha Badrinarayan Christopher Delaney Laura Hanrahan Arafat Mansur Jennifer Moiseff Stephen Park Marc Schwartz Trevor Sell Natalie Trzcinski Joseph Zenga

Presentation Schedule

Date & Topic	Tuesday, 9:00-9:50am B104 Comstock	Tuesday, 12:20-1:10pm B106 Comstock	Tuesday, 1:25-2:15pm B106 Comstock	Tuesday, 2:30-3:20pm B106 Comstock	Tuesday, 3:35-4:25pm G37 Plant Science
Sept 4 - NE & methods	Jin	Liz	Mike	Bernard	Trevor
Sept 11 - Glu excit & stroke	Stacey	Theo	Steve S.	Kaitlynn	Natalie
Sept 18 - 5HT & suicide	Bess	Jen B.	Dana	Kelly & Lexi	Christopher
Sept 25 - Cocaine ant.	Jules	Justin	Beth	Patrick	Joe
Oct 2 - Hallucinogen	Amanda & Rekha	Rachel & Adrienne	Jonathan	Adam B.	Laura
Oct 9 - NONE
Oct 16 - Marij. & synap.	Neha	Emily	Abby S.
Oct 23 - Opiate addict.	Gracielle	Jayan	Dimtry & Divya	Melanie	Arafat
Oct 30 - Placebo & analg.	Wing Kay & Kate G.	Max	Nick	Andrew	Steve P.
Nov 6 - Alcoholism	Dan B.	Lorelei	Vanessa	Sara
Nov 13 - Anxiolytics	Jason	Dan R.	Kate	Tara	Jen M.
Nov 20 - Antidepressants	TBA	Abby P.	Scott	Josh	Aneesha
Nov 27 - Schizophrenia	Dovie & Lily	Molly	Danielle	Jessica	Mark

 

Discussion Section Questions

Note: for the papers given below, all you have to do is to type in the Pubmed ID number in the search box of Pubmed, and you will get directly to the paper. Then click on “Get It! Cornell” or else the box with the name of the publisher, and follow directions to get to the PDF.  For legal anti-copyright reasons, it is best that you download your own copies.

Week of Aug. 27: Problem set on use of PubMed and Science Citation Index: see separate handout.

Week of Sept. 3: Methods to identify transmitter actions in the brain
Question: You would like to determine whether norepinephrine (NE) has any effects on neurons in the cerebellum.  Briefly describe several possible experimental methods that can be used to answer each of the following questions, and be prepared to discuss their relative strengths and weaknesses:

1. What kind of NE receptors are present in the cerebellum?
2. Are there receptors for NE on Purkinje neurons, the major output neurons from the cerebellum?
3. Is NE released during normal activity in the cerebellum?

Reading:  Meyer and Quenzer, Psychopharmacology, Chapter 4 “Methods of research in neurobehavioral pharmacology”, pp. 90-105.

Week of Sept.10:Glutamate excitotoxicity in stroke
Question:  It is widely thought that brain damage after an ischemic stroke is in part caused by excessive release of glutamate, and resulting excitotoxicity.  However, treatments based on controlling glutamate’s actions have been unsuccessful to date. How would you go about coming up with a new treatment, which would be useful after a stroke (and not just before it), which is based directly or indirectly on blocking excitotoxicity?

Reading: A.S. Hazell, “Excitotoxic mechanisms in stroke: An update of concepts and treatment strategies”.  Neurochemistry International 50: 9410953 (2007). Pubmed ID: 17576023.

Week of Sept.17: Serotonin and suicide
Question:  There is a correlation between low levels of serotonin function in the brain and impulsive violent or suicidal behavior in humans.  How would you design a study to determine whether a genetic defect in serotonin biochemistry is a contributing factor to suicidal behavior?

Week of Sept. 24: Cocaine antagonists
Question: The dopamine transporter (DAT) appears to be an essential target for cocaine reward and addiction.  It is known that cocaine binds to a different site on the DAT than dopamine does, raising the possibility that we could develop “cocaine antagonists” that block cocaine from binding and having an effect on the DAT while still allowing it to transport dopamine normally.  This would be a great drug for treatment of cocaine addiction. If a chemist gave you a series of possible candidate drugs, how would you design an experimental program to test whether any of them is actually a cocaine antagonist?

Reading: R. Chen, M.R. Tilley et al, “Abolished cocaine reward in mice with a cocaine-insensitive dopamine transporter.”  P.N.A.S. 103: 9333-9338 (2006).  Pubmed ID: 16754872

Week of Oct. 1: Hallucinogen targets in the brain
Question:  It is now clear that hallucinogens like LSD act through a common target of the 5HT2A receptor, but how this causes hallucinations is unknown.  One major question is where drugs like LSD are acting in the human brain. Design an experimental approach to answering this question.

Reading:N.D. Volkow et al., “Relationship between subjective effects of cocaine and dopamine transporter occupancy.” Nature 386: 827-830.  Pubmed ID: 9126740

Interested students should also read Vollenweider F.X. et al., “Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis.”  Neuropsychopharmacology 16: 357-372 (1997). Pubmed ID9109107

Week of Oct. 8: No discussion: Fall Break

Week of Oct. 15: Marijuana and synaptic plasticity
Question:  Evidence is growing that the endogenous endocannabinoid system plays a role in accelerating the extinction of certain types of memory.  You hypothesize that this may work by an endocannabinoid-mediated reversal of LTP.  Given a perfect experimental set-up of a single presynaptic neuron and a single postsynaptic neuron that can synthesize endocannabinoids, design a neurophysiological study to test your hypothesis.

Reading:  T. Tzounopoulos et al., “Co-activation of pre-and postsynaptic signaling mechanisms determines cell-specific spike-timing dependent plasticity.”  Neuron 54: 291-301  Pubmed ID:17442249

Week of Oct. 22: Opiate addiction and gene regulation
Question: Using microarray analysis, several studies have looked at changes in gene expression during chronic morphine treatment and upon morphine withdrawal.  All these studies show many genes that are either up- or down-regulated as a result of chronic morphine.  How would you go beyond this listing to figure out what the various genes are doing in response to morphine or during withdrawal, or whether any of these genes are involved in long-term sensitization and craving in recovering addicts?

Reading:  McClung C.A. et al., “Regulation of gene expression by chronic morphine and morphine withdrawal in the locus coeruleus and ventral tegmental area.” J. Neurosci. 25: 6005-6015 (2005).  Pubmed ID15976090

FOR BACKGROUND READ: Chao J. and E. J. Nestler, “Molecular neurobiology of drug addiction” Ann. Rev. Medicine 55:113-132 (2004) Pubmed ID14746512

Week of Oct.29: Placebo-mediated analgesia
Question:  A number of studies have shown that placebo treatments can reduce the perception of pain, and that the placebo effect is mediated by activation of the endogenous opioid peptide system.  Placebo effects can even be specific to one part of the body and not others.  With your knowledge of the pathways in the brain mediating pain and analgesis, how would you go about identifying the sites in the brain where the placebo effect occurs?

Reading: Benedetti F et al., “Somatotopic activation of opioid systems by target-directed expectations of analgesia”  J. Neurosci. 19: 3639-3648 (1999).  Pubmed ID10212322

Week of Nov. 5: Pharmacological therapies for alcoholism
Question: Several drugs are now in use for treatment of craving for alcohol in recovering alcoholics, while pre-clinical data suggest that others might also be useful.  What are the mechanisms by which these drugs might block the craving that leads to relapse to alcoholism?

Reading:   M. Heilig and M. Egli, “Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms.”  Pharmacol. THer. 111: 855-876 (2006).  Pubmed ID: 16545872

A. Chippitelli et al., “Cannabinoid CB1 receptor antagonism reduces conditioned reinstatement of ethanol-seeking behavior in rats.  Eur. J. Neurosci.  21: 2243-2251 (2005).  Pubmed ID15869521

Week of Nov. 12: Development of Novel Anxiolytics
Question: Pre-clinical studies have implicated the peptide Corticotropin Releasing Factor (CRF) in stress and fear responses in animals.  Preliminary studies suggest a possible correlation between CRF and post-traumatic stress disorder (PTSD).  Propose a general experimental plan to further test the relationship between CRF and anxiety disorders, combining animal and human studies.

Reading:  V. B. Risbrough and M. B. Stein, “Role of corticotropin releasing factor in anxiety disorders: a translational research perspective.”  Hormones and behavior, 50: 550-561 (2006).  Pubmed ID 16870185.

Week of Nov. 19:  Antidepressants, trophic factors and neurogenesis
Question: Preliminary studies have suggested that one mechanism of action of antidepressants is to enhance adult neurogenesis in the hippocampus, and that tropic factors such as BDNF and VEGF may be involved.  Design a study that would test this hypothesis using animal models for clinical depression.

Reading: J. L. Warner-Schmidt and R. S. Duman, “Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment.”  Hippocampus, 16: 239-249 (2006). Pubmed ID 16425236.

Week of Nov. 26: Genetic and developmental factors in schizophrenia
Question: DISC1 has been identified in several genetic screens as a candidate gene associated with schizophrenia and affective disorders.  It seems to have several roles, both during development and in adult signaling pathways.  Using an animal model, design a mutational study that would help to understand the relative importance of these different roles in the etiology of schizophrenia.

Reading:  S. Mackie et al., “Role of DISC1 in neural development and schizophrenia.”  Curr.  Opin. Neurobiol. 17: 95-102 (2007).  Pubmed ID 17258902

See also: S. J. Clapcote et al., “Behavioral phenotypes of Disc1 missense mutations in mice.”  Neuron 54: 387-402 (2007).