Press release

 

A pharmacological link between epilepsy and anxiety?

Paris, October 11, 2001

 


Is there a link between epilepsy and anxiety? It seems that such a link exists. This conclusion is based on the work of a group led by Georges Chapouthier, CNRS Research Director, and Patrice Venault, lecturer at Paris 5 University. Their research has been carried out in the framework of the "Vulnerabilité, adaptation et psychopathology" (Vulnerability, adaptation and psychopathology) research unit of the CNRS and Paris 6 and 7 Universities, located at La Pitié-Salpêtrière Hospital.


Epilepsy is a pathological tendency to have convulsions, whose relation to a major inhibiting brain neurotransmitter, GABA, has long been known to scientists. It acts as a cerebral brake, which, by blocking the circulation of nerve impulses, prevents the brain from short-circuiting. A short-circuit of sorts is precisely what occurs in epilepsy following insufficient GABA activity. Many treatments for epilepsy use molecules that increase GABA activity.

Anxiety, a normal phenomenon when it is moderate, can also become pathological. It has been shown that anxiety is also related to GABA: the very molecules that counteract the activity of GABA produce anxiety when administered in average doses and cause convulsions when administered in high doses. Using one of the molecules that counteract GABA activity, beta-CCM, which, depending on the dose, causes either anxiety or seizures, the researchers were able to show the correlation between epilepsy and anxiety.

For their experiment, Georges Chapouthier, Patrice Venault and their team members selected two strains of mice, one highly resistant and the other highly sensitive to beta-CCM, a convulsant in high doses and a generator of anxiety at lower doses. The researchers selected ten couples of mice that convulsed rapidly after being injected with the product, and ten couples that did not experience seizures after the same treatment.

Within a few generations, they obtained two strains of mice, one of which was highly resistant to beta-CCM (BR), and the other highly sensitive (BS). The two groups underwent three series of tests classically used to measure degrees of anxiety. The tests, carried out in collaboration with Jean Constentin's laboratory in Rouen, France, placed the mice in the following situations:
1 - An elevated maze containing an enclosed space and a space that opens on to a drop. The animal moves freely in the maze. If it spends more time in the open space it is considered to be experiencing no anxiety.
2 - The "light/dark" test: the animal can choose between two connected plexiglass boxes, one of which is clearly lit and the other, dark. Preference for the dark area implies a state of anxiety.
3 - The staircase test: this involves a small wooden staircase with five steps. The mouse climbs freely, and makes rearing movements as it climbs. The number of steps climbed is compared to the number of times the mouse rears. A significant amount of rearing behavior without any increase in the number of steps climbed implies a high degree of anxiety.

The results of the tests showed that there are considerable differences between the two strains but also revealed reactions that are contrary to what could have been expected. The BR group (resistant to beta-CCM) proved to have a higher degree of anxiety, while the BS group, with a higher sensitivity to the convulsion-causing properties of beta-CCM, had a lower degree of anxiety. One possible interpretation of this "inverse correlation" is that the BR strain is more sensitive to the spontaneous anxiety-causing effects while the BS strain is more sensitive to the convulsant effects of beta-CCM.

Even though many issues concerning the interpretation of the details and the analysis of the underlying mechanisms have still to be addressed, these results nevertheless suggest that in mice there is a strong physiological correlation between the mechanisms that control epileptic convulsions and certain forms of anxiety. Further studies should show if this correlation is also valid for humans.

Reference: Trends in Pharmacological Sciences, volume 22, no 10, October 2001, pp 491-493.


Researcher contacts:
"Vulnérabilité, adaptation et psychopathologie" Research Unit
Georges Chapouthier
Tel: +33 1 40 77 97 05
e-mail: chapout@ext.jussieu.fr
Patrice Venault
Tel: +33 1 40 77 98 31
e-mail: venault@ext.jussieu.fr

Press contact :
Martine Hasler
Tel : +33 1 44 96 46 35
e-mail : martine.hasler@cnrs-dir.fr