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Background and Purpose Excitatory amino acid transporters ( EAATs) in the CNS contribute to the clearance of glutamate released during neurotransmission. The aim of this study was to explore the role of EAATs in the regulation of locus coeruleus ( LC) neurons by glutamate. Experimental Approach We measured the effect of different EAAT subtype inhibitors/enhancers on glutamate- and KCl-induced activation of LC neurons in rat slices. EAAT2-3 expression in the LC was also characterized by immunohistochemistry. Key Results The EAAT2-5 inhibitor DL-threo-β-benzyloxaspartic acid (100 μM), but not the EAAT2, 4, 5 inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (100 μM) or the EAAT2 inhibitor dihydrokainic acid ( DHK; 100 μM), enhanced the glutamate- and KCl-induced activation of the firing rate of LC neurons. These effects were blocked by ionotropic, but not metabotrobic, glutamate receptor antagonists. DHK (100 μM) was the only EAAT inhibitor that increased the spontaneous firing rate of LC cells, an effect that was due to inhibition of EAAT2 and subsequent AMPA receptor activation. Chronic treatment with ceftriaxone (200 mg·kg−1 i.p., once daily, 7 days), an EAAT2 expression enhancer, increased the actions of glutamate and DHK, suggesting a functional impact of EAAT2 up-regulation on the glutamatergic system. Immuhistochemical data revealed the presence of EAAT2 and EAAT3 surrounding noradrenergic neurons and EAAT2 on glial cells in the LC. Conclusions and Implications These results remark the importance of EAAT2 and EAAT3 in the regulation of rat LC by glutamate. Neuronal EAAT3 would be responsible for terminating the action of synaptically released glutamate, whereas glial EAAT2 would regulate tonic glutamate concentrations in this nucleus. [ABSTRACT FROM AUTHOR]

Pre- and post-dispersal Helleborus foetidus (Ranunculaceae) seed predation by mice Apodemus sylvaticus as well as post-dispersal seed removal by ants was studied, during two years, in six plant populations within three geographical regions (Caurel, Cazorla and Mágina) of the Iberian Peninsula. An observational approach revealed strong interregional differences in seed predation by mice during the pre-dispersal phase, with high and similar rates of predation in Cazorla and Mágina and much lower rates in Caurel. There were also significant inter-annual variations on pre-dispersal seed predation by mice, while the existing habitat-related differences (of lower magnitude) were not consistent across regions. Field experiments based on seed-offering exclosures, showed that, despite some interregional variation, post-dispersal seed removal by ants was consistently high through all spatial and temporal scales considered, with most seeds being removed within 48 h. Conversely, post-dispersal seed predation by mice was highly variable among regions, being very high in Cazorla and minimal or absent in Caurel and Mágina. Interestingly, in Cazorla, in presence of mice, the number of seeds removed was rather independent of the presence/absence of ants, while under mice exclusion, it was determined by the presence/absence of ants. Conversely, in Caurel, the number of seeds removed by each remover agent (ants or mice) was independent of the presence/absence of the other agent. Thus, though uniquely in Cazorla, mice limited the number of seeds available to ants and, therefore, in this region could potentially have interfered on the development of seed traits that enable ants to efficiently harvest them. Our results support the notion that geographical variation over the Iberian Peninsula of mice seed predation may have promoted a mosaic of well-matching and mismatching situations between H. foetidus diaspore traits and the characteristics of ant communities, which is consistent with some recent theories on the geographical structure of interactions. [ABSTRACT FROM AUTHOR]

Cocaine not only increases brain dopamine levels but also activates the sigma 1 receptor (σ 1 R) that in turn regulates orexigenic receptor function. Identification of interactions involving dopamine D 1 (D 1 R), ghrelin (GHS-R 1a ), and σ 1 receptors have been addressed by biophysical techniques and a complementation approach using interfering peptides. The effect of cocaine on receptor functionality was assayed by measuring second messenger, cAMP and Ca 2+ , levels. The effect of acute or chronic cocaine administration on receptor complex expression was assayed by in situ proximity ligation assay. In silico procedures were used for molecular model building. σ 1 R KO mice were used for confirming involvement of this receptor. Upon identification of protomer interaction and receptor functionality, a unique structural model for the macromolecular complex formed by σ 1 R, D 1 R, and GHS-R 1a is proposed. The functionality of the complex, able to couple to both Gs and Gq proteins, is affected by cocaine binding to the σ 1 R, as confirmed using samples from σ 1 R -/- mice. The expression of the macromolecular complex was differentially affected upon acute and chronic cocaine administration to rats. The constructed 3D model is consistent with biochemical, biophysical, and available structural data. The σ 1 R, D 1 R, and GHS-R 1a complex constitutes a functional unit that is altered upon cocaine binding to the σ 1 R. Remarkably, the heteromer can simultaneously couple to two G proteins, thus allowing dopamine to signal via Ca 2+ and ghrelin via cAMP. The anorexic action of cocaine is mediated by such complex whose expression is higher after acute than after chronic administration regimens., (© 2021 Society for the Study of Addiction.)