TL neuro

July 2, 2015

CPDD 2015: Sex as a biological variable and pitfalls for behavioral studies

Filed under: Animal Models, CPDD, SABV — mtaffe @ 10:18 am

Cora Lee Wetherington presented on the new NIH initiative on sex as a biological variable (SABV) at the Animals-in-Research forum at the recent CPDD meeting held at the Arizona Biltmore.

Dr. Wetherington has long headed up NIDA’s operations on Sex/Gender differences in substance abuse research and is therefore a key voice on how the NIH will be responding to this new SABV initiative.

Her main point was to outline the elements of the new approach to sex-differences, starting with the Clayton and Collins editorial and leading up to the NOT-OD-15-102 Consideration of Sex as a Biological Variable in NIH-funded Research. This NOT warns NIH applicants that applications submitted after Jan 25, 2015 will need to take new steps in considering SABV.

In the Q&A after Dr. Wetherington’s presentation, Mike Bardo (lab website) asked a deceptively simple question. He wanted to know if people ran their male and female rats in different operant boxes. The point being that male rats might smell something related to the presence of a female in the box just prior to his session, or vice versa. This might have an effect that differed in some way from the presence of a same-sex rat. Bardo indicated that many labs try to have a set of operant boxes that are dedicated to each sex, perhaps even in separate experimental rooms, but intimated that this may become impractical in the new order of SABV after Jan 25, 2015.

Simple question, right? Well, this plays right into the determination of how practical it will be to tell behavioral pharmacology people to start running studies with both sex of rats. The immediate response to the SABV initiative is to say “This will double our experiment size!”. And this comment is rapidly followed by “Wait, by the time we consider female rat cycle, we are not just doubling the experment but possibly increasing our number of groups by 4-fold or more.”.

And indeed several prior questions directed at Dr. Wetherington touched on such issues.

The Bardo question, however, is an even more practical one of experimental throughput. Any given lab is going to be more inflexible in experimental equipment than in the sex of rats it chooses to run from month to month or year to year. Operant boxes are expensive and experimental space to house them is very dear. One cannot just outfit a parallel series of rooms to run the opposite sex. This is going to require compromises. It is going to involve more unknown variability introduced into the design. And it is going to be expensive merely to estimate this variability so as to come up working rules of thumb to address the problem raised by Mike Bardo.

I jumped up to try to emphasize the following points although I am not sure that Wetherington understood what I was driving at.

There are several options available to a lab like mine, if it wants to start running both male and female groups. First, we could do it entirely sequentially. Only females for a 3-4 month interval, then males, etc. This is less than ideal because if we are comparing the sexes, we would like to hold other variables constant. Cohorts run at the approximately the same time has a better chance of doing this. Second, we could run them in different rooms but this has a limit. We only have so many operant box testing rooms and this is typically far too few to accomplish all that we would like to accomplish in a perfect way. (For example, we simply cannot run all of our rats starting at the same exact time of day, relative to their light cycle. Totally impractical.) We have a lot of different projects going on at one time and lining them all up so that males are in one room and females another would slow overall progress. Third, we could keep some boxes within a room for males and some for females. This isn’t much better than separate rooms for operational flexibility purposes and it adds the additional factor of subjects being able to smell (and possible hear the ultrasonic vocalizations of) adjacent animals (the boxes are vented to/from room air). Fourth, we could run the sexes in sequence throughout the day with an extra dose of box cleaning and bedding changing in between the sexes. It adds some work, but preserves a great deal of flexibility.

But really, and getting back to Bardo’s question, we want to know if it matters if we run male and female rats in the same boxes. If it doesn’t, then all of my objections are moot.

So I was trying to point out to Wetherington how much effort it would take for just one of our experimental models to determine if there even were effects of mixed-sex operations on the rats’ behavior that needed to be accommodated. This is at least six months or a year of experiments, running to the tune of tens of thousands of precious direct costs from our NIH grants, to even begin to estimate the kind of variability that would be introduced by running male and female rats in a study within the same limited number of operant boxes. This is methodological work. Not work that can be easily risked by just launching off into the “real” study that is intended to be done.

How tolerant will grant review panels be of proposals that do not address these matters? How tolerant will they be of proposals that do address these matters seriously but plan to burn the first year on such methodological minutia?

How many reviwers will insist on “perfect” design (no females and males run in the same boxes or even housed in the same vivarium room!) regardless of whether it is necessary?

This is just one tiny, tiny, minute methodological question in a restricted subfield of investigation. How many similar questions apply to all of the research funded by the NIH that is poised to come under the SABV dictum seven months from now?

June 30, 2015

The primary translational product of drug-abuse science is information

Filed under: CPDD, Op/Ed, Public Health — mtaffe @ 11:16 am

This is an excerpt of a CPDD News and Views piece* that has been accepted for publication in Drug & Alcohol Dependence. I’ve been working on this idea for several years now and it has gone through various iterations. The list of people I need to thank for shaping my thinking on this since discovering the “science blog” around 2006 or so is long and I will no doubt forget some of them. Nevertheless, I am particularly indebted to David Kroll, Janet Stemwedel, Peter Lipson, Jessica Palmer, Isis the Scientist, DrugMonkey, Bethany Brookshire, Zen Faulkes, Virginia Hughes, J. David Jentsch, Allyson Bennett and Carl Hart. I participated in a Media Forum at the 2014 CPDD annual meeting and made a presentation which touched on many of these themes.

Drug Abuse Scientists Should Use Social Media to Engage the Public Because Their Primary Translational Product is Information


Increasing numbers of people are relying on the Internet to rapidly provide health information and preliminary medical diagnoses on the basis of key word searches (Jones and Fox 2009; Lagu et al. 2008; Moretti et al. 2012). In the most recent survey the Pew Internet & American Life project found that 59% of adults in the US had looked online for health information and 35% had gone online to gain information on a specific medical issue (Fox 2013; Fox and Duggan 2013). It is hardly news that exposure to high budget entertainment, informational and advertising media can influence the nonmedical use of psychotropic drugs (Brown and Witherspoon 2002; Nunez-Smith et al. 2010). However, current social media tools and the near universal use of Web searches to find information on health-related topics provide a new opportunity for individual scientists to communicate more directly with the lay public, health care providers and policy makers at the expense of minimal time and effort. This is of particular interest since so much of the most readily available information on psychotropic drugs is poorly informed by the existing scientific knowledge and may be substantially influenced by sociopolitical biases or agendas. Drug abuse scientists should therefore use social media to engage the public in a discussion of their ongoing scientific results.

Substance Abuse Information on the Internet

“When we confronted him, my teenage son assured me that he had done extensive research on the Internet which confirmed that pot is totally harmless”

-neighbor of Dr. Taffe, Aug 2011


June 18, 2012

CPDD 2012 Links

Filed under: CPDD — mtaffe @ 9:41 am

The CPDD blog by Marc Kaufmann has a number of summary posts up so far:

NIDA Director Volkow’s opening comments

The Bath Salts / Synthetic Cathinone Symposium organized by Annette Fleckenstein and myself.

The Public Policy forum in which the undoubling of the budget back to 2002 purchasing power and the 18% grant funding rate were mentioned.

Dirk Hanson (2012 CPDD Media Award recipient) from Addiction Inbox:

Nora Volkow’s comments on NIDA priorities.

Brief Notes/Pull Quotes

Blog at