The Effect of Chronic Treatment with Lacosamide and Topiramate on Cognitive Functions and Impaired Emotional Responses in a Pilocarpine-induced Post-status Epilepticus Rat Model

Folia Med (Plovdiv). 2020 Dec 31;62(4):723-729. doi: 10.3897/folmed.62.e51473.

Abstract

Introduction: Epilepsy and antiepileptic drugs can affect negatively the cognitive abilities of patients.

Aim: The present study aimed to evaluate the effect of topiramate (TPM) and lacosamide (LCM) on the emotional and cognitive re-sponses in naive animals and in animals with pilocarpine-induced status epilepticus.

Materials and methods: Male Wistar rats were randomly divided into 6 groups and status epilepticus was evoked in half of them by a single i.p. administration of pilocarpine (Pilo) (320 mg/kg): Pilo-veh, Pilo-TPM (80 mg/kg) and Pilo-LCM (30 mg/kg). Matched naive rats were treated with the same doses as follows: C-veh, C-TPM, and C-LCM. In a step-down passive avoidance test, the learning session was held for one day, the early retention test was conducted on day 2, and the long-term memory test - on day 7. Motor activity and anxiety were evaluated in an open field test.

Results: The Pilo-TPM and Pilo-LCM groups increased the time spent on the platform compared to Pilo-veh animals while the C-LCM animals decreased the time compared to C-veh animals during short- and long-term memory retention tests. TPM and LCM exerted an anxiolytic effect in naive rats. The two antiepileptic drugs were unable to alleviate the hyperactivity, but they alleviated the impulsivity associated with decreased anxiety level in epileptic rats.

Conclusions: Our findings suggest that LCM and TPM have a beneficial effect on cognition both in naive and epileptic rats. While the two antiepileptic drugs can produce an anxiolytic effect in naive rats, they alleviate the impulsivity after pilocarpine treatment.

Keywords: anxiety; cognition; epilepsy; lacosamide; topiramate.

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage
  • Cognition* / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Emotional Regulation* / drug effects
  • Follow-Up Studies
  • Lacosamide* / administration & dosage
  • Male
  • Pilocarpine / toxicity
  • Rats
  • Rats, Wistar
  • Status Epilepticus* / chemically induced
  • Status Epilepticus* / drug therapy
  • Status Epilepticus* / physiopathology
  • Time Factors
  • Topiramate* / administration & dosage

Substances

  • Anticonvulsants
  • Lacosamide
  • Pilocarpine
  • Topiramate