Behavioral and Neurochemical Consequences of Pentylenetetrazol-Induced Kindling in Young and Middle-Aged Rats

Abstract

(1) Objectives: Epilepsy disorder is likely to increase with aging, leading to an increased incidence of comorbidities and mortality. In spite of that, there is a lack of information regarding this issue and little knowledge of cognitive and emotional responses in aging subjects following epileptogenesis. We investigated whether and how aging distress epilepsy-related behavioral and biochemical outcomes are associated with cognition and emotion. (2) Methods: Young and middle-aged Wistar rats (3 or 12 months old) were treated with pentylenetetrazol (PTZ, 35 mg/kg) and injected on alternated days for 20 (young rats) and 32 days (middle-aged rats). Kindling was reached after two consecutive stages 4 plus one stage 5 or 6 in Racine scale. Control and kindled rats were evaluated in the elevated plus-maze (EPM) and object-recognition tests and their hippocampus was collected 24 h later for mitogen-activated protein kinases (MAPK) dosage. (3) Results: Middle-aged rats presented a higher resistance to develop kindling, with a decrease in the seizure severity index observed following the 4th and 9th PTZ injections. Middle-aged rats displayed an increased duration of the first myoclonic seizure and an increased latency to the first generalized seizure when compared to younger rats. The induction of kindling did not impair the animals’ performance (regardless of age) in the object-recognition task and the EPM test as well as it did not alter the hippocampal levels of MAPKs. (4) Significance: Our findings reveal that, despite age-related differences during epileptogenesis, middle-aged rats evaluated after kindling performed similarly during discriminative learning and emotional tasks in comparison to young animals, with no alteration of hippocampal MAPKs. Additional investigation must be carried out to explore the electrophysiological mechanisms underlying these responses, as well as the long-term effects displayed after kindling.

Effect of repeated seizures on spatial exploration and immediate early gene expression in the hippocampus and dentate gyrus

“…However, these animals also engaged in enhanced bursts of running and travelled at greater velocities when entering the center area compared to the peripheral compartment of the open field—a response not seen in control animals ( Fournier et al, 2009 , Fournier et al, 2020 ). These findings are suggestive of heightened emotional or anxiety-related behaviours ( La-Vu et al, 2020 , Crawley, 1985 ) and is consistent with past work showing that PTZ kindling can alter emotional behaviour in rodents on other behavioural tasks ( Lamberty and Klitgaard, 2000 , Hoeller et al, 2017 , Erdogan et al, 2005 ). Behavioural alterations, such as anxiety, depression and impaired cognitive performance are frequently observed in people with epilepsy ( Tramoni-Negre et al, 2017 , Krishnan, 2020 ), and these impairments show correlation with reduced hippocampal IEG expression in animal models ( Botterill et al, 2014 , Fournier et al, 2013 , Kalinina et al, 2019 , Chawla et al, 2013 ).…”

Antagonism of Histamine H3 receptors Alleviates Pentylenetetrazole-Induced Kindling and Associated Memory Deficits by Mitigating Oxidative Stress, Central Neurotransmitters, and c-Fos Protein Expression in Rats

“…The retrieval memory impairment accompanied by PTZ chronic treatment was previously demonstrated in numerous previous studies in elevated plus maze (EPM) paradigm [2,33,[41][42][43] and several other behavioral tests, e.g., MWM paradigm [44][45][46]. In the current study, the procognitive effect of H3R antagonist E177 (5 and 10 mg/kg, i.p.)…”

Retrieval-Induced Forgetting in a Pentylenetetrazole-Induced Epilepsy Model in the Rat

“…Nevertheless, exploratory behavior was not affected by kindling, as the total exploration time was similar to that of the saline-treated rats in the sample phase and in the test phase. Also, object recognition memory was not affected by kindling, as both groups were able to recognize the familiar object in the control phase of the task, findings similar to what is reported by Hoeller and colleagues [43].…”