86). Nociceptin/orphanin FQ potency was enhanced in slices prepared from rats previously subjected to a 15 min swim stress (EC50 = 1.98 +/- 0.11 nM). Swim stress did not change the number or affinity of NOP receptors in DRN. Stress-elicited potentiation involved corticotropin-releasing factor (CRF)(1) receptors, GABA signaling and protein synthesis, being attenuated by pre-treatment with antalarmin (20 mg/kg, i.p.), diazepam (2.4 mg/kg, see more i.p.) and
cycloheximide (2.5 mg/kg, i.p.), respectively. In anesthetized unstressed rats, locally applied nociceptin/orphanin FQ(0.03 and 0.1 ng/30 nl) inhibited the firing rate of DRN neurons (to 80 +/- 7 and 54 +/- 10% of baseline, respectively). Nociceptin/orphanin FQ inhibition was potentiated both 24 h after swim stress and I h after CRF (30 ng/30 nl intra-DRN). Stress-induced potentiation was prevented by the selective CRF(1) receptor antagonist, NBI 30755 (20 mg/kg, i.p.). In contrast, the inhibitory response of DRN neurons to the 5HT(1A) agonist, 8CH-DPAT (1 mu g/1 mu l, intra-DRN) was not potentiated by swim stress, ruling out a nonspecific enhanced permeability of GIRK channel. Together, these findings suggest that CRF buy S63845 and the nociceptin/orphanin FQ/NOP system interact in the DRN during stress to control
5HT transmission: this may play a role in stress-related neuropsychopathologies. (C) 2009 Elsevier Ltd. All rights reserved.”
“Background: It has been widely accepted that glial pathology and disturbed synaptic transmission contribute to the neurobiology of depression. Apart from monoaminergic alterations, an influence of glutamatergic signal transduction has been reported. Therefore, gene expression of glutamate transporters that strictly control synaptic glutamate concentrations have to be assessed out in animal models of stress and depression.
Methods: We performed in situ-hybridizations in learned helplessness rats, a well established animal model of depression, to assess vGluT1 and
EAAT1-4. Sprague-Dawley rats of two inbred lines were tested for helpless behavior and grouped into three cohorts according to the number of failures to stop foot shock currents by lever pressing.
Results: Helpless animals showed a significantly suppressed expression of the glial glutamate transporter EAAT2 (rodent nomenclature GLT1) in hippocampus and cerebral cortex compared to littermates with low failure rate and not helpless animals. This finding was validated on protein level using immunohistochemistry. Additionally, expression levels of EAAT4 and the vesicular transporter vGluT1 were reduced in helpless animals. In contrast, the transcript levels of EAAT1 (GLAST) and EAAT3 (EAAC1) were not significantly altered.
Conclusions: These results strongly suggest reduced astroglial glutamate uptake and implicate increased glutamate levels in learned helplessness.