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When URB597 was administered during late-adolescence, it ameliorated ELS-induced depression- and anxiety-like behavior. Moreover, in males, ELS and URB597 decreased CB1r levels in the prefrontal cortex (PFC) and CA1 and GRs in the PFC and basolateral amygdala (BLA). In females, ELS and URB decreased CB1r in the BLA and GRs in the CA1 and BLA. The findings suggest that mid-adolescence, as opposed to late-adolescence, may not be a potential developmental period for chronic treatment with FAAH inhibitors and that sex-dependent alterations in CB1r and GRs expression in the BLA-PFC-CA1 circuit may contribute to the depressive behavioral phenotype.Substance P (SP) regulates inhibitory synaptic transmission mediated by GABAA receptors in the cerebral cortex; however, SP-mediated regulation of excitatory synaptic transmission remains poorly understood. Artenimol NF-κB inhibitor We performed whole-cell patch-clamp recordings from pyramidal neurons to examine the effects of SP on excitatory postsynaptic currents (EPSCs) mediated via AMPA receptors in the insular cortex (IC), which is involved in nociceptive information processing. First, EPSCs evoked by minimal electrical stimulation (eEPSCs) including stepwise EPSCs and failure events, were examined. SP dose-dependently suppressed mean eEPSC amplitude, partially due to an increase in the failure rate of eEPSCs. The SP-induced suppression of eEPSCs was accompanied by an increase in the paired-pulse ratio and was inhibited by the preapplication of SR140333, an NK1 receptor antagonist. [Sar9,Met(O2)11]-substance P, an NK1 receptor-selective agonist, mimicked the effects of SP on eEPSCs and decreased the frequency of miniature EPSCs (mEPSCs) without changing the average mEPSC amplitude. Considering that most NK1 receptors in the cerebral cortex are expressed in nitric oxide synthase (NOS)-positive GABAergic neurons, the SP-induced suppressive effect on EPSCs may be mediated by nitric oxide (NO) in this subtype of GABAergic neurons. NO imaging using the fluorescent probe DAX-J2 Red supports this hypothesis SP increased the fluorescence intensity of DAX-J2 Red in some GABAergic neurons. Furthermore, both L-NAME, an NOS inhibitor, and PTIO, an NO scavenger, diminished the SP-induced suppression of eEPSCs. These results suggest that the activation of presynaptic NK1 receptors contributes to SP-induced eEPSC suppression by activating the NO synthesis pathway in GABAergic neurons. (246 words).Inhibitory circuits in the basolateral nuclear complex of the amygdala (BNC) critical for controlling the acquisition, expression, and extinction of emotional responses are mediated by GABAergic interneurons (INs). Studies in rodents have demonstrated that separate IN subpopulations, identified by their expression of calcium-binding proteins and neuropeptides, play discrete roles in the intrinsic circuitry of the BNC. Far less is known about IN subpopulations in primates. In order to fill in this gap in our understanding of primate INs, the present investigation used dual-labeling immunohistochemistry for IN markers to identify subpopulations expressing cholecystokinin (CCK), calbindin (CB), calretinin (CR), and somatostatin (SOM) in somata and axon terminals in the monkey BNC. In general, colocalization patterns seen in somata and axon terminals were similar. It was found that there was virtually no colocalization of CB and CR, the two calcium-binding proteins investigated. Three subtypes of CCK-immunoreactive (CCK+) INs were identified on the basis of their expression of CR or CB (1) CCK+/CR+; (2) CCK+/CB+); and (3) CCK+/CR-/CB-. Almost no colocalization of CCK with SOM was observed, but there was extensive colocalization of SOM and CB. CCK+, CR+, and CCK+/CR+ double-labeled axon terminals were seen surrounding pyramidal cell somata in basket-like plexuses, as well as in the neuropil. CB+, SOM+, and CB+/SOM+ terminals did not form baskets, suggesting that these IN subpopulations are mainly dendrite-targeting neurons. In general, the IN subpopulations in the monkey are not dissimilar to those seen in rodents but, unlike rodents, CB+ INs in the monkey are not basket cells.Deficits in the anticipation and experience of affective events represent a key risky factor for a variety of mental disorders, such as anxiety and depression. Here, we examined temporal dynamics underlying the modulations of the aversive mood state on neural responses of anticipating and perceiving affective pictures. Participants were asked to perform an affective cueing paradigm in both threat and safe contexts. In the task, a cue (S1) signaled the subsequent presentation of positive/negative event (e.g., happy or fearful faces) as an affective target stimulus (S2), and participants were instructed to indicate their subjective feelings in response to the target stimuli while electroencephalography (EEG) was recording. Our findings revealed that threat context compared with the safe context attenuated the contingent negative variation (CNV) responses to the cues of positive expressions, and decreased differential late positive potential (LPP) responses to the perception of negative and positive events. These findings suggest that aversive mood dampens the anticipation of positive events and inhibits the elaboration of negative events. The current findings do not only advance our understanding on the temporal characteristics of affective anticipation and experience but also have implications on the emotional deficits across various mental disorders characterized by chronic mood disturbances.Auto-regulation mechanisms in serotonergic neurons regulate their electrical activity and secretion. Since these neurons release serotonin from different structural compartments - including presynaptic terminals, soma, axons and dendrites - through different mechanisms, autoregulation mechanisms are also likely to be different at each compartment. Here we show that a chloride-mediated auto-inhibitory mechanism is exclusively localized at presynaptic terminals, but not at extrasynaptic release sites, in serotonergic Retzius neurons of the leech. An auto-inhibition response was observed immediately after intracellular stimulation with an electrode placed in the soma, in neurons that were isolated and cultured retaining an axonal stump, where presynaptic terminals are formed near the soma, but not in somata isolated without axon, where no synaptic terminals are formed, nor in neurons in the nerve ganglion, where terminals are electrotonically distant from the soma. Furthermore, no auto-inhibition response was detected in either condition during the longer time course of somatic secretion.