NOP Receptor Agonist Ro 64-6198 Decreases Escalation of Cocaine Self-Administration in Rats Genetically Selected for Alcohol Preference

Cocaine dependence is a psychiatric condition for which effective medications are still lacking. Published data indicate that an increase in nociceptin/orphanin FQ (N/OFQ) transmission by NOP receptor activation attenuates cocaine-induced place conditioning and the locomotor sensitization effects of cocaine. This suggests that the activation of the N/OFQ receptor (NOP) may attenuate the motivation for psychostimulants. To further explore this possibility, we investigated the effect of the potent and selective NOP receptor agonist Ro 64-6198 on cocaine intake under 1 h short access (ShA) and 6 h long access (LgA) operant self-administration conditions in rats. We used Marchigian Sardinian alcohol-preferring (msP) rats and Wistar control rats. msP rats were used because we recently found that this rat line, originally selected for excessive alcohol drinking and preference, exhibits a greater propensity to escalate cocaine self-administration following LgA training. msP rats are also characterized by innate overexpression of the N/OFQ-NOP system compared with Wistar rats. Wistar and msP rats both exhibited an increase in cocaine self-administration under LgA conditions, with a higher trend toward escalation in msP rats. In Wistar rats, the intraperitoneal administration of Ro 64-6198 (0. 1 and 3 mg/kg) significantly decreased ShA cocaine self-administration. In Wistar rats that underwent LgA cocaine self-administration training, Ro 64-6198 induced no significant effect either during the first hour of self-administration or after the entire 6 h session. In msP rats, Ro 64-6198 significantly reduced cocaine self-administration both under ShA conditions and in the first hour of the LgA session. At the end of the 6 h session, the effect of Ro 64-6198 was no longer observed in msP rats. The highest dose of Ro 64-6198 (3 mg/kg) did not affect saccharin self-administration in msP rats but reduced saccharin self-administration in Wistar rats. Altogether, these data suggest that NOP receptor activation attenuates cocaine self-administration, and this effect tends to be more pronounced in a rat line with innately higher NOP receptor expression and that more robustly escalates cocaine intake

Selective inhibition of phosphodiesterase 7 enzymes reduces motivation for nicotine use through modulation of mesolimbic dopaminergic transmission

Approximately 5 million people die from diseases related to nicotine addiction and tobacco use each year. The nicotine-induced increase of corticomesolimbic dopaminergic (DAergic) transmission and hypodopaminergic conditions occurring during abstinence are important for maintaining drug-use habits. We examined the notion of reequilibrating DAergic transmission by inhibiting phosphodiesterase 7 (PDE7), an intracellular enzyme highly expressed in the corticomesolimbic circuitry and responsible for the degradation of cyclic adenosine monophosphate (cAMP), the main second messenger modulated by DA receptor activation. Using selective PDE7 inhibitors, we demonstrated in male rats that systemic PDE7 enzyme inhibition reduced nicotine self-administration and prevented reinstatement to nicotine seeking evoked by cues or by the pharmacological stressor yohimbine. The effect was also observed by direct application of the PDE7 inhibitors into the nucleus accumbens (NAc) shell but not into the core. Inhibition of PDE7 resulted in increased DA- and cAMP-regulated neuronal phosphoprotein and cAMP response element-binding protein and their phosphorylated forms in the NAc. It also enhanced the DA D1 receptor agonism-mediated effects, indicating potentiation of protein kinase A–dependent transmission downstream of D1 receptor activation. In electrophysiological recordings from DA neurons in the lateral posterior ventral tegmental area, the PDE7 inhibitors attenuated the spontaneous activity of DA neurons. This effect was exerted through the potentiation of D1 receptor signaling and the subsequent facilitation of c-aminobutyric acid transmission. The PDE7 inhibitors did not elicit conditioned place preference and did not induce intravenous self-administration, indicating lack of reinforcing properties. Thus, PDE7 inhibitors have the potential to treat nicotine abuse

Application of Enhanced Recovery after Surgery in Interventional Treatment of Tracheal Malignant Tumor

Currently, enhanced recovery after surgery (ERAS) has been widely accepted by surgery and anesthesiology all over the world, and applied in colorectal surgery, gynecology, liver surgery, breast surgery, urology and spinal surgery. But ERAS are rarely used in the field of interventional bronchoscopy. In recent years, more and more researchers have begun to explore the application of ERAS in bronchoscopic interventional therapy. This article discussed that preoperative preparation, anesthesia, intraoperative operation, postoperative observation and other aspects can influence interventional bronchoscopy

Analysis and Calculation of Threshold Pressure Gradient Based on Capillary Bundle

Oilfield water injection is one of the important means to supplement energy to the formation and enhance oil recovery in the process of oilfield development. The level of water injection technology determines the effect of oilfield development and also determines the length of oilfield development life. Research on seepage law of water injection development in low-permeability reservoir is the basis and important technical means of low-permeability reservoir development, and the key point of seepage law is to analyze the starting pressure gradient law. In previous studies, either static test or dynamic experimental value is used, so the error of pseudo starting pressure gradient derived from experimental value is too large, which makes people expand the starting pressure value in low-permeability reservoir in practical engineering application, and the starting pressure gradient obtained from laboratory test cannot be applied in actual reservoir. To accurately calculate the threshold pressure gradient for low-permeability reservoirs, the threshold permeability is proposed through the study of the seepage law and laboratory experiments. It is recognized that the threshold pressure gradient and the threshold permeability had been changing during the seepage. Through steady-state “flow rate-pressure difference” displacement experiment, with natural cores from a low-permeability reservoir, based on a capillary bundle model, the method for calculating the gradient is innovatively proposed. The experimental data show that the whole low-permeability seepage flow is nonlinear, divided into three stages according to the physical stages with obvious changes. Through processing and analyzing of the experimental results, first, it is showed that both threshold pressure gradient and threshold permeability increase with the rise of flow rate and the increasing amplitude is gradually decreasing. Second, the study proposes the permeability is the main controlling reason of the threshold pressure gradient, and the flow velocity is an important reason. Third, we obtain the formulas of the minimum threshold pressure gradient, the threshold pressure gradient, and the corresponding threshold permeability of different cores and the power function relationship between the threshold pressure gradient and the core permeability is obtained. And further, the one-dimensional experimental results are applied to the radial fluid flow, and the recognition that the threshold pressure gradient decreases with increasing distance and the ratio of the threshold pressure to the total displacement pressure difference are obtained. The ratio of starting pressure to total pressure drop is about 0.5, and the higher the permeability is, the lower the ratio is lower under 0.5. These findings significantly help in understanding how to effectively develop low-permeability reservoir by water injection. Through the dynamic macro experiment and microcapillary bundle principle, the experiment can be divided into several sections for analysis, which can be more accurate. The minimum start-up pressure gradient can not only guide the later development of the oilfield, but also enrich the theoretical study of non-Darcy low-velocity seepage. At the same time, the law of flow velocity and start-up pressure gradient indirectly proves the boundary layer theory of the generation mechanism of start-up pressure gradient and supports and guides the effective development of various development methods of low-permeability reservoir