The PTZ kindling mouse model of epilepsy exhibits exploratory drive deficits and aberrant VTA dopamine neuron activity in both familiar and novel space.

The PTZ kindling mouse model of epilepsy exhibits exploratory drive deficits and aberrant VTA dopamine neuron activity in both familiar and novel space. Behav Brain Res. 2017 May 12;: Authors: Ahmadi M, Dufour JP, Seifritz E, Mirnajafi-Zadeh J, Saab BJ Abstract Recurrent seizures that define epilepsy are often accompanied by psychosocial problems and cognitive deficits with incompletely understood aetiology. We therefore used the pentylenetetrazol (PTZ) kindling model of epilepsy in mice to examine potential seizure-associated neuropathologies, focusing on motivation, memory and novel-environment-induced activation of midbrain dopaminergic neurons. In addition to recurrent seizures, we found that PTZ kindling led to a strong suppression of novelty-driven exploration while largely sparing fear-driven exploration. The deficits in exploratory drive may be relevant for other cognitive impairments since reduced unassisted rearing in a learning arena correlated with poorer spatial memory of object location. Using c-Fos immunofluorescence as a marker of neuronal activity, we observed that dopamine neurons within the ventral tegmental area (VTA) of PTZ kindled mice demonstrate hyperactivity at baseline, and exhibit a blunted response to a novel environment compared to saline-injected cagemate controls. These data extend previous findings of PTZ kindling-mediated disruptions of hippocampal processes important for novel environment recognition...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research