Acid-sensing ion channel 1a regulates the specificity of reconsolidation of conditioned threat responses.

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 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.

The Involvement of Intra-Hippocampal Dopamine Receptors in the Conditioned Place Preference Induced By Orexin Administration into the Rat Ventral Tegmental Area.

The activity of dopamine (DA)-containing neurons in the ventral tegmental area (VTA) is a key mechanism in mesolimbic reward processing that has modulatory effects on different diencephalic structures like hippocampus (HIP), and receives inhibitory feedback and excitatory feed forward control. In addition, within the hippocampus, DA receptors are mostly located in the dorsal part (CA1) and dopaminergic innervations are predominant in this sub-region. The current study aimed to examine the effect of intra-hippocampal CA1 administration of SCH23390 and Sulpiride as D1- and D2-like receptor antagonists on the acquisition of orexin-induced conditioned place preference (CPP), respectively. Cannulas were unilaterally implanted into the VTA and HIP of adult male albino Wistar rats weighing 200-250 g. For induction of CPP, orexin A (10 ng/0.3 µL saline) was daily microinjected into the VTA during a three-day conditioning phase. Thereafter, various doses of SCH23390 and Sulpiride (0.25, 1 and 4 µg) were unilaterally injected into the CA1 during this 3-day conditioning phase after intra-VTA administration. The conditioning score was then calculated. Results revealed that intra-CA1 administration of D1- and D2-like receptor antagonists during the 3-day conditioning phase attenuated the acquisition of place preference by orexin A in a dose-dependent manner. It seems the effect of D2-like receptor antagonist within the CA1 region of hippocampus on this phenomenon was found to be more considerable than that of D1-like receptor antagonist. It is concluded that orexin-induced CPP may be mediated, at least in part, by stimulation of DA receptors in the CA1.

Post-stroke neuronal circuits and mental illnesses.

Stroke is one of the leading causes of death in the United States. It is also associated with severe mental illnesses, such as depression and anxiety, that hinder the rehabilitation of surviving patients. Thus, a better understanding of how stroke causes mental illnesses is crucial, but little is known about the neurological mechanisms involved. In this review, we summarized the most common mental illnesses developed after stroke, as well as the underlying mechanisms at the neuronal circuit level.

Evaluation of Antioxidant Activity of R. Slooffiae, R. Mucilaginosa Extracts.

INTRODUCTION: Antioxidants 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. METHODS: To 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. RESULTS: The 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. CONCLUSION: It 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.

Differential roles of orexin receptors within the dentate gyrus in stress- and drug priming-induced reinstatement of conditioned place preference in rats.

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.

Differential effects of intra-accumbal orexin-1 and -2 receptor antagonists on the expression and extinction of morphine-induced conditioned place preference in rats.

Orexinergic neurons originate from the hypothalamic nuclei, sending projections toward mesolimbic regions such as the nucleus accumbens (NAc). In this study, an attempt was made to determine the effects of intra-accumbal administration of SB334867 as an orexin-1 receptor (OX1R) antagonist and TCS OX2 29 as an orexin-2 receptor (OX2R) antagonist in the expression and maintenance of morphine-induced conditioned place preference (CPP) in rats. One hundred and five adult Wistar rats weighing 200-280g were bilaterally implanted with cannulae into the NAc. During the 3-day conditioning phase, animals received daily subcutaneous administration of morphine (5mg/kg). CPP score and locomotor activity of animals were recorded by Ethovision software. Different doses of bilateral injections of the OX1R and OX2R antagonists (3, 30 and 300µg/0.5µl DMSO) were administered just before the conditioning test or daily injection during extinction phase. Our finding revealed that intra-accumbal administration of OX1R not OX2R antagonist just before the CPP test attenuated the expression of the morphine-induced CPP. However, the blockade of these two kinds of receptors shortened the extinction phase in the rats. This effect was more significant in intra-NAc OX1R antagonist-treated animals. The results suggested that OX1R within the NAc may be necessary for the morphine-induced expression. Additionally, it seems that the existence of the orexin receptors in the NAc was important for the maintenance of morphine rewarding properties during the extinction phase. Therefore, orexins may be considered as a promising therapeutic agent in preventing the expression and maintenance of morphine rewarding effects on dependent individuals.