Orexin and cannabinoid systems modulate long-term potentiation of the hippocampus CA1 area in anesthetized rats.

Objectives: Long-term potentiation (LTP) is a kind of synaptic plasticity and has a key role in learning and memory. Endocannabinoids and orexins are the endogenous systems that can modulate synaptic plasticity. Given that new studies have shown an interaction between cannabinoid and orexin systems in the brain, we decided to examine this interaction between the two systems on LTP induction in rat's hippocampus. Materials and Methods: Twenty-eight male Wistar rats were used for evaluating the effects of co-administrating of cannabinoid-1 receptor (CB1R) antagonist (AM251) and orexin-2 receptor (OX2R) antagonist (TCS OX2 29) on the induction of LTP in the Schaffer collateral-CA1 synapses of rat hippocampus. The drugs were microinjected into the CA1 area of rat hippocampus 30 min before inducing of LTP. Results: Results showed that sole administration of the antagonists inhibited LTP, with respect to the control group. Also, co-administrating of them reduced LTP as compared to the control group, but not significantly more than that when the antagonists were solely microinjected into the CA1. Nonetheless, the inhibitory effect of concurrent administration of the antagonists on LTP lasted until the end of the recording. Conclusion: These results propose that endogenous cannabinoids and orexins play a role in the expression of LTP, at least by CA1-CB1Rs and CA1-OX2Rs, respectively. Finally, there is no interaction between CB1R and OX2R on the induction of LTP in the Schaffer collateral-CA1 synapses; therefore, these two systems possibly act through common signaling pathways in the hippocampus's CA1 region.

Mutual assistance of nucleus accumbens cannabinoid receptor-1 and orexin receptor-2 in response to nicotine: a single-unit study.

BACKGROUND AND PURPOSE: The nucleus accumbens (NAc) express both orexin-2 receptor (OX2R) and cannabinoid receptor type 1 (CB1R). Orexin and cannabinoid regulate the addictive properties of nicotine. In this study, the effect of the CB1R blockade on the electrical activity of NAc neurons in response to nicotine, and its probable interaction with the OX2R in this event, within this area, were examined via the single-unit recording. EXPERIMENTAL APPROACH: The spontaneous firing rate of NAc was initially recorded for 15 min, and then 5 min before subcutaneous injection of nicotine (0.5 mg/kg)/saline, AM251 and TCS-OX2-29 were injected into the NAc. Neuronal responses were recorded for 70 min, after nicotine administration. FINDINGS/RESULTS: Nicotine excited the NAc neurons significantly and intra-NAc microinjection of AM251 (25 and 125 ng/rat), as a selective CB1R antagonist, prevented the nicotine-induced increases of NAc neuronal responses. Moreover, microinjection of AM251 (125 ng/rat), before saline injection, could not affect the percentage of change of the neuronal response. Finally, simultaneous intra-NAc administration of the effective or ineffective doses of AM251 and TCS-OX2-29 (a selective antagonist of OX2R) prevented the nicotine- induced increases of NAc neuronal responses, so that there was a significant difference between the group received ineffective doses of both antagonists and the AM251 ineffective dose. CONCLUSION AND IMPLICATIONS: The results suggest that the CB1R can modulate the NAc reaction to the nicotine, and it can be concluded that there is a potential interplay between the OX2R and CB1R in the NAc, in relation to nicotine.

Electrophysiological study of the response of ventral tegmental area non-dopaminergic neurons to nicotine after concurrent blockade of orexin receptor-2 and cannabinoid receptors-1.

The ventral tegmental area (VTA) is a key brain region, involved in the dependency on nicotine. Studies have shown that orexin and cannabinoids are likely to play an important role in nicotine dependency. In this study, the effect of orexin receptor-2 (OX2R) and cannabinoid receptor-1 (CB1R) blockade were investigated in response to nicotine in male rats, on the neural activity of VTA. Nicotine was injected subcutaneously and its effect on the firing of VTA non-dopaminergic (ND) neurons was investigated, using in vivo extracellular single unit recording. Nicotine increased the ND neuronal activity of the VTA. AM251 (0.18, 0.9, 1.8 nmol/0.3 µL), as a selective cannabinoid CB1R antagonist, and TCS-OX2-29 (0.5, 1, 5 nmol/0.3 µL), as a selective OX2R antagonist, individually or simultaneously were microinjected into the VTA. The results revealed that blockade of OX2R and CB1R in the VTA could prevent the increased firing rate, caused by nicotine. Concurrent administration of TCS-OX2-29 and AM251 could decrease responsiveness of VTA-ND neurons to nicotine, but it did not show a greater response than their single application. Because the synergistic effect was not observed in the simultaneous blockade of these two receptors, therefore, in order to detect the interactions of these two receptors, further studies are needed in the field of intracellular signaling.

Orexin type-2 receptor blockade prevents the nicotine-induced excitation of nucleus accumbens core neurons in rats: An electrophysiological perspective.

BACKGROUND: The nucleus accumbens core (NAcc) expresses both orexin and nicotinic acetylcholine receptors (nAChRs). Orexin is among important neurotransmitters, which regulates addictive properties of drugs of abuse including nicotine. The role of orexin-2 receptor (OX2R) in the regulation of NAcc neural activity in response to nicotine has not yet been studied. Hence, in this study, we examined whether the OX2R antagonist (TCS-OX2-29) can adjust the effects of nicotine on electrical activity of NAcc neurons, in urethane-anesthetized rats, using the single unit recording. METHODS: Neuronal firing of NAcc was recorded for 15 min, then TCS-OX2-29 (OX2R-antagonist; 1, 3 and 10 ng/rat) or DMSO were microinjected into NAcc, just 5 min before subcutaneous (sc) administration of nicotine (0.5 mg/kg) or saline. The spontaneous firing activity was recorded for 70 min, after nicotine injection. RESULTS: The results demonstrated that nicotine significantly excites the NAcc neurons and interestingly, the administration of TCS-OX2-29 (3 and 10 ng/rat) into the NAcc, inhibited nicotine-induced increases of NAcc neuronal responses. Furthermore, administration of TCS-OX2-29 (10 ng/rat), just 5 min before sc administration of saline instead of nicotine, did not significantly alter the neuronal responses, compared to the saline-control group. CONCLUSION: Our results showed that, although OX2R blockade alone did not affect neuronal activity in the NAcc, it was able to prevent the exciting effects of nicotine on NAcc neuronal activity. Therefore, we proposed that orexin has a potential modulator effect, in response to nicotine.

Functional crosstalk of nucleus accumbens CB1 and OX2 receptors in response to nicotine-induced place preference.

In the present study, we have evaluated the existence of functional interaction between orexin-2 receptor (OX2R) and cannabinoid-1 receptor (CB1R) in the nucleus accumbens core (NAcc), in nicotine-induced conditioned place preference (CPP) of Wistar male rat. Nicotine (0.5 mg/kg; s.c.) in the course of conditioning, produced a significant place preference, without any effect on the locomotor activity. Intra-NAcc administration of ineffective and effective doses of TCS-OX2-29 (2 and 6 ng/rat), a selective OX2R antagonist and AM251 (10 and 50 ng/rat), a selective CB1R antagonist, showed a significant interaction between OX2R and CB1R in the acquisition of nicotine-induced CPP (p < 0.01), and the locomotor activity (p < 0.05). No significant interaction was observed between these two receptors in the expression of nicotine-induced CPP. Our findings provide insight into the possible interaction of OX2R and CB1R of the NAcc in nicotine addiction. We propose a potential interaction between cannabinoid and orexinergic systems within the NAcc, in producing the rewarding effects.

Effects of concurrent blockade of OX2 and CB1 receptors in the ventral tegmental area on nicotine-induced place preference in rats.

In this study, the role of orexin-2 (OX2) and cannabinoid-1 (CB1) receptors and their potential interaction within the ventral tegmental area (VTA) on nicotine-induced place preference, was examined in male rats. A 5-day conditioned place preference (CPP) paradigm was used. Nicotine (0.5 mg/kg; s.c.) induced a significant CPP, without any effect on the locomotor activity during the testing phase. TCS-OX2-29 (0.4, 0.8 and 4 µg/rat), as a selective OX2 receptor antagonist and AM251 (0.2, 1 and 2 µg/rat), as a selective cannabinoid CB1 receptor antagonist, individually or simultaneously were microinjected bilaterally into the VTA. The results showed that administration of AM251 (1 and 2 µg/rat) or TCS-OX2-29 (0.4, 0.8 and 4 µg/rat) into the VTA, during the 3-day conditioning phase or testing day, could dose-dependently inhibit the development of nicotine-induced CPP, in the acquisition or expression, respectively. Concurrent administration of ineffective doses of TCS-OX2-29 and AM251 into the VTA could not affect conditioning scores. The findings of this study support the possible role of OX2 and CB1 receptors in the VTA, in the acquisition and the expression of nicotine-induced place preference. Furthermore, our data suggest that there is a possible interaction between the VTA orexinergic and cannabinoid systems in nicotine-induced place preference.

Nephrogenic acute respiratory distress syndrome: A narrative review on pathophysiology and treatment.

The kidneys have a close functional relationship with other organs especially the lungs. This connection makes the kidney and the lungs as the most organs involved in the multi-organ failure syndrome. The combination of acute lung injury (ALI) and renal failure results a great clinical significance of 80% mortality rate. Acute kidney injury (AKI) leads to an increase in circulating cytokines, chemokines, activated innate immune cells and diffuse of these agents to other organs such as the lungs. These factors initiate pathological cascade that ultimately leads to ALI and acute respiratory distress syndrome (ARDS). We comprehensively searched the English medical literature focusing on AKI, ALI, organs cross talk, renal failure, multi organ failure and ARDS using the databases of PubMed, Embase, Scopus and directory of open access journals. In this narrative review, we summarized the pathophysiology and treatment of respiratory distress syndrome following AKI. This review promotes knowledge of the link between kidney and lung with mechanisms, diagnostic biomarkers, and treatment involved ARDS induced by AKI.