Orexins are hypothalamic peptides involved in the modulation of the feeding, arousal, reward function, learning, and memory; nevertheless, the role of orexins in stress and relapse are largely unclear. Therefore, in the present study, the reinstatement model were used to examine the effects of intradentate gyrus (DG) administration of SB334867 as an orexin-1 receptor antagonist and TCS OX2 29, as an orexin-2 receptor antagonist on drug priming- and forced swim stress (FSS)-induced reinstatement of morphine. One-hundred and 44 adult male albino Wistar rats weighing 200 g-280 g were bilaterally implanted by cannulas into the DG. For induction of conditioned place preference (CPP), subcutaneous (sc) injection of morphine (5 mg/kg) was used daily during a 3-day conditioning phase. Then, the conditioning score (conditional stimulus [CS]) was calculated. After a 24 hr "off" period following achievement of extinction criterion, rats were tested for drug priming-induced reinstatement by priming dose of morphine (1 mg/kg, sc) and for FSS-induced reinstatement 10 min after FSS. In the next experiments, animals received different doses of intra-DG administration of SB334867 and TCS OX2 29 (3, 10, and 30 μg/0.5 μl 12% DMSO per side), bilaterally and were subsequently tested for morphine priming- and FSS-induced reinstatement. Our findings indicated that the FSS-induced the reinstatement of seeking behaviors. Furthermore, intra-DG administration of orexin-1 and orexin-2 receptor antagonists attenuated drug priming-induced reinstatement dose-dependently. However, they have trivial role in FSS-induced reinstatement. It is concluded that drug priming-induced reinstatement may be mediated, at least in part, by stimulation of orexin receptors in the DG.

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IntroductionAntioxidants are health beneficial compounds that can protect cells and macromolecules from the damage of reactive oxygen species (ROS). The aims of this study were to compare the total antioxidant and carotenoid production in R. Slooffiae and R. Mucilaginosa.MethodsTo isolate the carotenoid pigment, cells were suspended in acetone and broken using a homogenizer, followed by centrifugation, and supernatant was separated. For analytical method, pigments were measured spectrophotometrically at 450 nm. The B-carotene bleaching and 1, 1-diphenyl-2-picrylhdrazyl (DPPH) assay were used to determine antioxidant properties of R. Slooffiae and R. Mucilaginosa by measuring the decrease in absorbance at 470 and 517 nm.ResultsThe results showed that the content of total carotenoid in R. Slooffiae was higher than R. Mucilaginosa and it presented higher ability to show antioxidant activity. The mean total antioxidant activity of ascorbic acid was the highest (97.11 ± 6.11%), followed by BHT (64.71 ± 5.41%), R. sloofias extract (57.91 ± 7.34%) and R. Mucilaginosa (39.32 ± 5.85%). The EC50 of ascorbic acid was the strongest (0.252 ± 0.000 mg/ml), followed by BHT (0.612 ± 0.009 mg/ml) and R. Slooffiae (0.658 ± 0.033 mg/ml). There was significant difference observed between the EC50 of R. Slooffiae and BHT.ConclusionIt was found that both strains have ability to produce carotenoid and show antioxidant ability; however, R. Slooffiae had more potential in producing carotenoid and showing antioxidant ability than R. Mucilaginosa. Further study is required, in order to utilize this strain in the food, pharmaceuticals and cosmetics industries.

Reconsolidation has been considered a process in which a consolidated memory is turned into a labile stage. Within the reconsolidation window, the labile memory can be either erased or strengthened. Manipulating acid-sensing ion channels (ASICs) in the amygdala via carbon dioxide (CO2) inhalation enhances memory retrieval and its lability within the reconsolidation window. Moreover, pairing CO2 inhalation with retrieval bears the reactivation of the memory trace and enhances the synaptic exchange of the calcium-impermeable AMPA receptors to calcium-permeable AMPA receptors. Our patch-clamp data suggest that the exchange of the AMPA receptors depends on the ubiquitin-proteasome system (UPS), via protein degradation. Ziram (50 µM), a ubiquitination inhibitor, reduces the turnover of the AMPA receptors. CO2 inhalation with retrieval boosts the ubiquitination without altering the proteasome activity. Several calcium-dependent kinases potentially involved in the CO2-inhalation regulated memory liability were identified using the Kinome assay. These results suggest that the UPS plays a key role in regulating the turnover of AMPA receptors during CO2 inhalation.

Recent research on altering threat memory has focused on a reconsolidation window. During reconsolidation, threat memories are retrieved and become labile.Reconsolidation of distinct threat memories is synapse-dependent whereas the underlying regulatory mechanism of the specificity of reconsolidation is poorly understood. We designed a unique behavioral paradigm in which a distinct threat memory can be retrieved through the associated conditioned stimulus. In addition, we proposed a regulatory mechanism by which the activation of acid-sensing ion channels (ASICs), strengthens the distinct memory trace associated with the memory reconsolidation to determine its specificity. The activation of ASICs by carbon dioxide (CO2) inhalation when paired with memory retrieval, triggers the reactivation of the distinct memory trace, resulting in greater memory lability. ASICs potentiate the memory trace by altering the amygdala-dependent synaptic transmission and plasticity at selectively targeted synapses. Our results suggest that inhaling CO2 during the retrieval event increases the lability of a threat memory through a synapse-specific reconsolidation process.