Pentylenetetrazol-induced seizure-like behavior and neural hyperactivity in the medicinal leech

Abstract

This study examined the capacity of a known pro-epileptic drug, pentylenetetrazol (PTZ), to elicit seizure-like activity in the medicinal leech, Hirudo verbana. During in vivo experiments, PTZ elicited increased motor activity in a concentration-dependent manner with the highest concentration (10 mM) eliciting episodes of highly uncoordinated exploratory and swimming behavior. Co-application of the anti-epileptic drug, phenytoin, failed to reduce the absolute amount of PTZ-induced motor behavior, but was able to prevent expression of abnormal exploratory and swimming behaviors. During in vitro experiments in which extracellular recordings of connective nerve activity were made, bath application of 1 μM PTZ in Mg(2+)-free saline elicited a significant increase in spontaneous activity. This PTZ-induced increase in activity was completely inhibited by phenytoin. Interestingly, PTZ-induced hyperactivity was also blocked by co-application of the endocannabinoid 2-arachidonoyl glycerol and the selective serotonin re-uptake inhibitor (SSRI) fluoxetine. These findings suggest that the leech can be a useful system in which to study potential anti-epileptic treatments.

A Systematic Review on Non-mammalian Models in Epilepsy Research

“…This is further supported by the similar physiological processes found in both leech and mammalian nervous systems in terms of neural circuitry and development. The maintenance and handling of leeches is also simpler and inexpensive as compared to mammalian models (Hahn and Burrell, 2015 ).…”

“…Only one study by Hahn and Burrell ( 2015 ) was conducted using the medicinal leech as an animal model in this review. They did this by first placing a single leech in a 100 ml beaker filled with 50 ml of pond water.…”

“…While the similarity of certain non-mammalian seizure like behaviors to human seizures (Lucey et al, 2015 ) is a great boon, the dissimilarity of these non-mammalian models to humans also ironically makes them ideal models. As an example, the non-mammalian models covered in this review typically have a relatively simpler CNS, yet retain much of the functionality and characteristics of their more complicated mammalian counterparts such as the major neurotransmission systems (Ramakrishnan et al, 2013 ) as well as neural circuitry and development (Hahn and Burrell, 2015 ). As the non-mammalian models covered in this review are relatively small, they can be easily and cheaply maintained in large numbers with little logistical and financial difficulties.…”