The role of hippocampal NMDA receptors in long-term emotional responses following muscarinic receptor activation

Extensive evidence indicates the influence of the cholinergic system on emotional processing. Previous findings provided new insights into the underlying mechanisms of long-term anxiety, showing that rats injected with a single systemic dose of pilocarpine--a muscarinic receptor (mAChR) agonist--displayed persistent anxiogenic-like responses when evaluated in different behavioral tests and time-points (24 h up to 3 months later). Herein, we investigated whether the pilocarpine-induced long-term anxiogenesis modulates the HPA axis function and the putative involvement of NMDA receptors (NMDARs) following mAChRs activation. Accordingly, adult male Wistar rats presented anxiogenic-like behavior in the elevated plus-maze (EPM) after 24 h or 1 month of pilocarpine injection (150 mg/kg, i.p.). In these animals, mAChR activation disrupted HPA axis function inducing a long-term increase of corticosterone release associated with a reduced expression of hippocampal GRs, as well as consistently decreased NMDAR subunits expression. Furthermore, in another group of rats injected with memantine--an NMDARs antagonist (4 mg/kg, i.p.)--prior to pilocarpine, we found inhibition of anxiogenic-like behaviors in the EPM but no further alterations in the pilocarpine-induced NMDARs downregulation. Our data provide evidence that behavioral anxiogenesis induced by mAChR activation effectively yields short- and long-term alterations in hippocampal NMDARs expression associated with impairment of hippocampal inhibitory regulation of HPA axis activity. This is a novel mechanism associated with anxiety-like responses in rats, which comprise a putative target to future translational studies

Behavioral profile and Fos activation of serotonergic and non-serotonergic raphe neurons after central injections of serotonin in the pigeon (Columba livia)

Central injections of serotonin (5-HT) in food-deprived/refed pigeons evoke a sequence of hypophagic, hyperdipsic and sleep-like responses that resemble the postprandial behavioral sequence. Fasting-refeeding procedures affect sleep and drinking behaviors "per se". Here, we describe the behavioral profile and long-term food/water intake following intracerebroventricular (ICV) injections of 5-HT (50, 150, 300 nmol/2 μl) in free-feeding/drinking pigeons. The patterns of Fos activity (Fos+) in serotonergic (immunoreactive to tryptophan hydroxylase, TPH+) neurons after these treatments were also examined. 5-HT ICV injections evoked vehement drinking within 15 min, followed by an intense sleep. These effects did not extend beyond the first hour after treatment. 5-HT failed to affect feeding behavior consistently. The density of double-stained (Fos+/TPH+) cells was examined in 6 brainstem areas of pigeons treated with 5-HT (5-HTW) or vehicle. Another group received 5-HT and remained without access to water during 2h after treatment (5-HTØ). In the pontine raphe, Fos+ density correlated positively to sleep, and increased in both the 5-HTW and 5-HTØ animals. In the n. linearis caudalis, Fos+ and Fos+/TPH+ labeling was negatively correlated to sleep and was reduced in 5-HTØ animals. In the A8 region, Fos+/TPH+ labeling was reduced in 5-HTW and 5-HTØ animals, was positively correlated to food intake and negatively correlated to sleep. These data indicate that hyperdipsic and hypnogenic effects of ICV 5-HT in pigeons may result from the inhibition of a tonic activity of serotonergic neurons, which is possibly relevant to the control of postprandial behaviors, and that these relationships are shared functional traits of the serotonergic circuits in amniotes.status: publishe

(A) Outline of the treatments and experimental schedule: saline (Sal, 0.9%) or pilocarpine (Pilo, 150 mg/kg). (B and C) Effects of pilocarpine on plasma levels of CORT (ng/ml) and ACTH (pg/ml) and (D) expression of GRs (85 and 117 kDa) in the hippocampus of rats injected with pilocarpine.

<p>Animals were euthanized 24 h or 1 month after treatments. Protein expression levels of GRs were determined by Western blotting analysis, quantified by densitometric scanning and expressed as a ratio of signal intensity for the target proteins relative to that for β-actin (43 kDa). Data are presented as mean±S.E.M. of 3–6 animals per group. Comparisons were made by Student´s t test. *p≤0.05 or **p<0.001 as compared with saline (control) group.</p

(A) Outline of the treatments and experimental schedule: memantine (Men, 4 mg/kg), saline (Sal, 0.9%) or pilocarpine (150 mg/kg). (B–C) Effects of memantine on the expression of NMDAR1 (120 kDa) and R2B (180 kDa) in the hippocampus of rats injected with pilocarpine.

<p>Animals were euthanized 24 h or 1 month after treatments. Protein expression levels of NMDARs were determined by Western blot analysis, quantified by densitometric scanning and expressed as a ratio of signal intensity for the target proteins relative to that for β-actin (43 kDa). Each group is represented by illustration of two lanes in order to denote intra-group variations. Data are presented as mean±S.E.M. of 3–6 animals per group. Comparisons were made by two-way ANOVA followed by Student–Newman–Keuls's test. *p≤0.05 or **p≤0.001 as compared with sal+sal group.</p

Posttranslational marks control architectural and functional plasticity of the nuclear pore complex basket

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