In my last post, I introduced you to one of my favorite kind of critters, the planarians, and went over some aspects of the changes in behavior that are induced on them by nicotine, a drug with widespread human abuse. It is remarkable that these worms, which look nothing like a human, can display behaviors reminiscent of people who use abused drugs. In a previous post, I briefly explored why.
In the last few years, planarians have been used to explore aspects of the behavioral effects of another widely abused drug, cocaine. Before going into that, we must first take a brief detour to your favorite dentist’s office (is it even possible to have a favorite dentist? But I digress . . .).
The development of anesthetic agents was a blessing for humanity. In my opinion, there is no better way of stating this. Close to 200 years ago, the only available anesthetic agents were several big guys who held the patient still and in place while the surgeon worked as fast as possible. This was also true, albeit less dramatically, in dental procedures. Interestingly, in those times dental interventions were done by the town’s barber, who also served as the town’s dentist. Moreover, dentists, not physicians, were the first to use anesthetic agents and develop the general field of anesthesia. Nowadays, local anesthetics are an essential component of dental and medical practice.
The first example of a compound showing local anesthetic properties was cocaine. In fact, its anesthetic effects were observed well before its addictive and toxic effects were recognized.
The history of the discovery of cocaine is an excellent example of how a naturally-occurring substance finds its way into medical applications. Cocaine is synthesized by various plant species of the genus Erythroxylum (it means reddish), which are widely distributed in parts of Central and South America. Natives named these plants “khoka” (which sounded like “coca” to the Spanish Conquistadores), which means “The” plant; this indicates the importance that was given to this plant in this native American culture. Most historians agree that coca leaves were used as early as 5,000 years ago. Natives chewed on them to take advantage of their mild stimulant effects.
The first written report alluding to the anesthetic properties of coca leaves was published in 1653. A Spanish priest, Bernabé Cobo, went to his barber to take care of a toothache. The barber told him that he’d rather not pull the tooth out since it seemed healthy enough, so, Father Cobo, on the advice of a fellow priest, started chewing on coca leaves. Lo and behold, after a few days, the pain was gone!
The actual chemical isolation of the main active principle in coca leaves, cocaine, was achieved by the German chemist Albert Niemann in 1860. Oddly, even though cocaine’s anesthetic properties were noted by various authors, it was not only until 1884 when cocaine was used in ophthalmologic and dental surgery. To this day, cocaine is still used in a limited way for certain type of surgeries, because in addition of being an anesthetic, cocaine also induces vasoconstriction, which limits excessive bleeding.
For some time, the only source of cocaine was the coca plant, as its chemical analysis and synthesis proved elusive. Artificially synthesized cocaine was finally obtained in 1923. Once the use of cocaine became widespread, (it was used in cough drops and even in children’s toothache drops) its toxicity and addictive properties became immediately apparent. Ironically, cocaine was thought to be useful against morphine addiction! This was proposed by no other than Dr. Sigmund Freud (who, by the way, was a neurologist, not a psychologist, and who was also the first “famous person” to become addicted to cocaine).
Back to planaria
The earliest reference that I have been able to find on the application of cocaine in research using planaria was published in 1891 in the journal The American naturalist, where they used cocaine to immobilize the worms for microscopical studies (if you know of any earlier reference, I would appreciate to get that information). The next report appeared in 1907, where the use of cocaine was reported to “narcotize” a new planaria species discovered in Hawaii.
After these works, no other cocaine/planaria reports were published until 1996-1997 (again, if you know of any, please send me the information), when an established planarian research group in Italy, led by Dr. Guido Palladini of the University of Rome, published two papers on the subject. One of them had a pharmacology/behavioral emphasis and a second one had an anatomical/morphological emphasis. The Palladini research group originally proposed planaria as an animal model in pharmacology as early as 1975 and published 20 papers on planarian pharmacology between 1975 and 2008. In 2001, a paper describing behaviors resembling “withdrawal symptoms” (a set of physiological and behavioral effects triggered by discontinuation of drug use) upon exposure to cocaine, was published by a group at Temple University in Philadelphia, Pennsylvania, led by Dr. Robert Raffa. Starting with this paper, a renewed interest in the pharmacological aspects of planaria research was rekindled. To date, Raffa’s group alone has published about 30% of the papers in planarian pharmacology between 2001 and 2011, out of a total of about 100 papers. Also there are several additional research groups with a specific interest in planarian pharmacology, including laboratories in Japan, Boston, California, Minnesota, New Jersey, UK and my own research group in Pennsylvania among others.
The use of planaria as a relatively unexplored animal model in terms of pharmacology has the potential to advance the field in unexpected ways, with the eventual possibility of developing compounds and treatments useful in clinical settings. We will explore some of these aspects in future posts. Thank you for reading!
If you want to know more:
Buttarelli FR, Pellicano C, Pontieri FE
Neuropharmacology and behavior in planarians: translations to mammals.
Comp Biochem Physiol C Toxicol Pharmacol. 2008 May;147(4):399-408. Epub 2008 Feb 1. Review
Calatayud J, González A
History of the development and evolution of local anesthesia since the coca leaf. Anesthesiology. 2003 Jun;98(6):1503-8.
Raffa RB and Rawls SM
Planaria: A Model for Drug Action and Abuse [Hardcover]
Landes Bioscience, Inc.; 1st edition (December 4, 2008)
Sarnat HB, Netsky MG
The brain of the planarian as the ancestor of the human brain.
Can J Neurol Sci. 1985 Nov;12(4):296-302.