Neuropharmacology
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Conditioned defeat is a model in Syrian hamsters (Mesocricetus auratus) in which normal territorial aggression is replaced by increased submissive and defensive behavior following acute social defeat. The conditioned defeat response involves both a fear-related memory for a specific opponent as well as anxiety-like behavior indicated by avoidance of novel conspecifics. We have previously shown that systemic injection of a 5-HT2a receptor antagonist reduces the acquisition of conditioned defeat. ⋯ We found that injection of MDL 11,939 into the BLA impaired acquisition of the conditioned defeat response and blocked defeat-induced anxiety in the open field, but did not significantly impair avoidance of former opponents in the Y-maze. Furthermore, we found that injection of TCB-2 into the BLA increased the acquisition of conditioned defeat and increased anxiety-like behavior in the open field, but did not alter avoidance of former opponents. Our data suggest that 5-HT2a receptor signaling in the BLA is both necessary and sufficient for the development of conditioned defeat, likely via modulation of defeat-induced anxiety.
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Despite more than 20 clinically approved antiepileptic drugs (AEDs), there remains a substantial unmet clinical need for patients with refractory (AED-resistant) epilepsy. Animal models of refractory epilepsy are needed for at least two goals; (1) better understanding of the mechanisms underlying resistance to AEDs, and (2) development of more efficacious AEDs for patients with refractory seizures. It is only incompletely understood why two patients with seemingly identical types of epilepsy and seizures may respond differently to the same AED. ⋯ Next we investigated the inter-individual variation in the anti-seizure effects of these AEDs and, in case of focal seizures, found responders and nonresponders to all AEDs except carbamazepine. Most nonresponders were resistant to more than one AED. Our data further validate the intrahippocampal kainate mouse model as a model of difficult-to-treat focal seizures that can be used to investigate the determinants of AED efficacy.