To further explore the mechanisms of FB1 neurotoxicity, we here investigated the effects of acute FB1 co-exposure with glutamate and in the low magnesium model of epilepsy on neuronal calcium
level, mitochondrial membrane potential, and cell death in glio-neuronal cultures. FB1 increased the glutamate-induced calcium signal in neurons and changed neuronal calcium signals to more sustained intracellular calcium rises in the low magnesium model of epilepsy click here that coincided with mitochondrial membrane potential depolarization. FB1 co-exposure increased the percentage of dead neurons in low magnesium conditions dose dependently when compared with low magnesium exposure only, whereas in FB1 and glutamate co-exposure neuronal death remained unchanged when compared with glutamate treatment only. Our results show that FB1 makes neurons more vulnerable to glutamate-induced toxicity and epileptiform conditions, indicating that FB1 can enhance the detrimental effect of these conditions on neurons. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Rationale Cocaine strengthens behaviors associated with its administration. The stress response by individuals that are defeated in a brief aggressive confrontation can also promote enduring behavioral consequences similar to those of stimulants.
Objectives The study intends
to find whether intermittent episodes of defeat promote cocaine’s reinforcing effects by triggering selleck chemical N-methyl-D-aspartic acid (NMDA)-receptor-mediated plasticity in the ventral tegmental area (VTA).
Materials and methods Long-Evans rats were investigated after four social defeats in three experiments. Two experiments examined systemic or intra-VTA antagonism of NMDA receptors during stress on the later expression of behavioral sensitization and cocaine self-administration during fixed E7080 and progressive ratio (PR) schedules of reinforcement (0.3 mg/kg/infusion), including a novel 24-h variable-dose continuous access binge (0.2, 0.4, and 0.8 mg/kg/infusion,
delivered in an irregular sequence). Third, the expression of receptor proteins NR1 (NMDA) and GluR1 [alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)] were examined in VTA and nucleus accumbens.
Results Intermittent defeats augment locomotor responses to cocaine and increase cocaine taking. Rates of responding during binges are increased after defeat stress. These effects are prevented when NMDA or AMPA receptor antagonists are administered before defeats. VTA infusions of the NMDA antagonist AP-5 (5 nmol/side) before stress prevents locomotor sensitization to cocaine and intensified responding for cocaine during a PR schedule or binge. Episodic defeats increase GluR1 AMPA subunit protein expression in the VTA.