Jesse Schank, Amy Anderson and Meera Modi
Originally published May 2008.
Some of the most interesting questions in neuropharmacology concern drugs of abuse, how they act, why people take them, and why people find it hard to stop taking them. With some exceptions, drugs of abuse are illegal, or “controlled”, substances. So how does one go about obtaining these chemicals for laboratory research? Are they grown in that greenhouse on the roof of the parking deck? Are they synthesized in a trailer behind the DUC? Are they purchased on a street corner downtown?
The U.S. government has a system of drug classification known as the “Schedule of Controlled Substances”, which consists of 5 levels. Inclusion in the schedule and level assignment is based loosely on severity of effects, medicinal value, and addictive properties, although most aspects of this ranking system are commonly debated. Some of these drugs are often prescribed clinically (for example, Valium) while others are used recreationally in the vast majority of cases (for example, cocaine).
To purchase controlled substances for laboratory research, a DEA license is required. This license must be faxed along with a special form to the distributor when ordering drugs for your lab. Most controlled substances can be obtained from drug companies such as Sigma. The DEA performs on-site inspections, usually every year or two, during which security procedures and usage records are assessed. The DEA also comes to Emory once or twice a year to collect and dispose of any unused controlled substances that have expired.
Controlled drugs must be stored in a locked drawer, cabinet, or safe when not in use. After weighing out drug to be used in an experiment, this amount must be logged along with the lot number on the drug vial, the date, and the specific experiment that the drug is to be used for. A separate log must be kept for each controlled substance used in the lab. All experiments where controlled substances are administered to animals must be approved by the Emory University Institutional Animal Care and Use Committee.
To maintain personal safety, follow all instructions listed on the vial and keep Material Safety Data Sheets for each substance on file in the lab. Wear appropriate personal protective equipment when handling controlled substances. This equipment is often listed on the drug vial. When administering the drug to animals, if an accident occurs such as a needle stick during injection, file a report with the Emory Environmental Health and Safety Office and follow their recommendations for treatment and monitoring of the injury.
Human subjects are often useful in neuroscience research so that scientists can explore areas of interest that are uniquely human, such as cognition, psychological issues, complex interpersonal relationships and specific com plex disease states. In such cases, an animal model may not exist or may not give us enough information, making human research necessary. Research in humans may also be the last step in a long line of translational research, which often begins in animals and ends with clinical drug trials in human subjects. In addition, human subjects can also be used in fMRI studies, observational studies, historical interviews, cognition and memory tests, longitudinal development studies (infant and child research), etc. Although using human subjects is crucial to the progress of medicine, science and sociology, certain rules must be followed to protect human participants.
THE GOLDEN RULE: Minimal Risk and Maximal Benefit
Each study must justify the use of human subjects by balancing the risk to the subjects and the benefits to society as a whole. Studies must always strive to minimize the risk to each participant. This can be done in the following ways:
1. Getting Consent: Ensure that the participant is a volunteer and is not coerced into participating in any way. Also, the subject must understand that she or he has to the right to leave at any time.
2. Ensuring Privacy: Any information gathered on human subjects must be kept confidential and measures must be taken to make sure information is properly stored and de-identified.
3. Health Dangers: Any health dangers must be minimized. If any dangers exist, the participant must be informed of them before they consent to participate.
4. Emotional Damage: Researchers must ensure that participation in the study does not cause emotional damage such as fear of certain stimuli, guilt over actions performed during the study, or negative memories associated with the study. These feelings can normally be combated by thoroughly explaining the study to the subject and giving them full disclosure about the study after their participation.
Autoradiography is a method for determining the spatial distribution of receptors within tissue. A specific ligand for a receptor is labeled with a radioactive element, generally 3H (tritium) or 125I. The ligand is either administered to the animal in in vivo autoradiography or applied directly to the tissue in in vitro autoradiography. The ligand binds to its receptor and the incorporated radioactive molecule emits ionizing radiation (usually β particles). These particles interact with the emulsion of photographic film, resulting in an image reflecting the receptor distribution profile. A similar technique is in situ hybridization, in which mRNA distribution is determined instead of receptor distribution. Complementary radiolabeled oligonucleotides are used as ligands to assess mRNA concentrations and even their locations within the cell. Through this technique, experimenters can gain knowledge of cellular protein synthesis and concentrations of receptors with nonspecific ligands.
List of Safety Concerns:
1. Be Neat: Keep all radioactive material (including all the labware) confined to one specific area that is labeled as a radioactive work zone
2. Be Aware: On the flip side, be aware of what you are doing in a radioactive work zone. Do not eat in or allow street clothes to come in contact with the radioactive area, as they can easily become contaminated and allow for the transfer of radioactive material outside of the lab. Also, remember that you can’t feel, smell, or taste radiation, so it’s important to keep that desk at which you eat your Hot Pockets free of 125I hot packets.
3. Be Conscientious: Dispose of all radioactive waste properly and account for all radioactive material, whether it was used in an experiment or transferred to a waste container. Do not share radioactive material between labs, no matter how much you like (or dislike) them, as this allows radioactivity to potentially become lost or unaccounted for.
4. Be Skeptical: Despite what you may hear from a certain subpopulation of fourth years, keep in mind that: it is not that cool, Ron Calabrese hasn’t done it and it won’t help you pass quals!
5. Don’t mouth Pipet!!!