Veratridine‐Induced Wet Dog Shake Behaviour and Apoptosis in Rat Hippocampus

Abstract

Abstract:We have previously evaluated veratridine as an in vitro model of seizure using conventional electrophysiological recordings in rat hippocampal CA1 pyramidal neurones. The aim of this investigation is to further characterize this convulsant as an in vivo model of seizure. Veratridine was administered intraperitoneally to male Fisher rats in a dose range of 100-400 mg/kg. Within 5 min. after the injections, the animals entered a quiescent period which was followed 10-15 min. later by facial automatism (washing), grooming, masticatory jaw movement and profuse salivation. This phenomenon was followed by the development of wet dog shake and forelimb clonus. The time (mean∫S.E.M.) for the onset of induction of these shakes for all tested doses was 31.65∫2.85 min. and the number of shakes (mean∫S.E.M.) 30 min. after the onset was 17.2∫2.85. The onset and number of wet dog shakes induced by veratridine was dose-dependent. No rat death was recorded until 2 weeks after the experiments. Histopathological studies of animals 2 weeks after veratridine administration showed evidence of apoptosis in the hippocampus. Our results indicate that veratridine produced a behavioural pattern of a limbic seizure which mimics temporal lobe epilepsy in man. Based on our previous findings in vitro and of this investigation in vivo, veratridine can be used as an experimental tool to evaluate potential antiepileptic drugs effective against this type of limbic behaviour.We have characterized the proconvulsant activity of veratridine in vitro in rat brain slices and conventional electrophysiological intracellular techniques in hippocampal CA1 pyramidal neurones (Tian et al. 1995). Veratridine (0.03-0.2 mM) caused no changes in the passive membrane parameters including the resting membrane potential and input resistance. These concentrations also induced a relatively slow, large, synaptic-independent potential called the slow depolarizing after-potential. Higher doses of veratridine (over 0.1 mM) induced bursting, or seizure-like activity after applying a brief super threshold intracellular stimulation (Tian et al. 1995). The duration of seizure-like activity bursting which can be up to 10 sec. was dependent on the amplitude of slow depolarizing after-potential, and not on the stimulus strength or duration. At 0.3 mM or higher concentration, veratridine induced spontaneous rhythmic bursting. Both veratridine-induced evoked or spontaneous rhythmic bursting were sensitive to membrane potential changes and independent of synaptic transmission (Otoom et al. 1998). This was evident when seizure activity persisted after complete blockade of evoked synaptic potential with kynurenic acid.The mechanism of veratridine-induced bursting activity in hippocampal CA1 pyramidal neurones revealed that veratridine accentuated the depolarizing rectification so that a

Depletion of 14‐3‐3 zeta elicits endoplasmic reticulum stress and cell death, and increases vulnerability to kainate‐induced injury in mouse hippocampal cultures

“…Veratridine‐induced neuronal death, like that of KA, is also associated with induction of p53 and apoptosis‐related signalling (Jordan et al. 2003; Otoom et al. 2006).…”

“…Accordingly, we examined ER stress and injury responses using an alternative seizure‐like injury. Veratridine, a sodium channel activator, induces hippocampal pyramidal neuron burst‐firing, seizures and neuronal death (Alkadhi and Tian 1996; Otoom et al. 2006).…”

“…Accordingly, we examined ER stress and injury responses using an alternative seizure-like injury. Veratridine, a sodium channel activator, induces hippocampal pyramidal neuron burst-firing, seizures and neuronal death (Alkadhi and Tian 1996;Otoom et al 2006). Treatment of hippocampal organotypic slices with 10 lM veratridine for 24 h caused cell death within CA3 and CA1 and to a lesser extent the granule cell layer of the DG, that was of similar magnitude to 5 lM KA over the same time frame ( Fig.…”

Puncture of a Lumbar Intervertebral Disc Induces Changes in Spontaneous Pain Behavior

“…36 -40 WDS has also been considered to indicate stress [41][42][43] and pain 44,45 and is regulated by 5-Ht-activation. [46][47][48] An increase in grooming and WDS may thus indicate that the rats experience some form of discomfort. If this is in anyway related to low back pain is not possible to understand from the present investigation.…”

Pain Behavior Changes Following Disc Puncture Relate to Nucleus Pulposus Rather than to the Disc Injury Per Se: An Experimental Study in Rats

“…Assessment of wet dog shakes (WDS) has been widely used in psychopharmacological studies and is a typical sign of withdrawal from opiates, benzodiazepines and barbiturates [10-14]. WDS has also been considered to indicate stress [15-17] and pain [18, 19] and is regulated by 5-Ht-activation [20-22]. Although it was not possible to draw any conclusions if grooming and WDS could correspond to disc induced low back pain, it was concluded that the findings seemed to indirectly support such hypothesis [1].…”