Assessing the Effect of Diazepam on Methamphetamine-induced Seeking Behavior in Rats

Background: Relapse is a common problem in substance-use disorders. Accumulating evidence has shown that diazepam can reduce the abuse potential of some drugs. Objectives: We investigated the effects of diazepam during and after the withdrawal period on the reinstatement of conditioned place preference (CPP) induced by a single dose of methamphetamine in male Wistar rats. Methods: Three groups of rats were trained to acquire methamphetamine CPP. The rats in the control group received, respectively, saline and methamphetamine (1 mg/kg, daily, ip) in the extinction and priming phases. Two other groups (one and two) had a similar process, but the rats in group one received diazepam (3 mg/kg, daily, ip) in the extinction phase and those in group 2 received a single dose of diazepam just before the priming phase. The CPP was checked daily during all processes. Results: We showed that a 3-day period injection of methamphetamine (1 mg/kg) resulted in a positive conditioning score on the first day after conditioning. Also, 3 mg/kg of diazepam daily in the extinction period shortened the withdrawal period for one day and extinction happened on the 9th and 10th days. Diazepam also reduced the conditioning score at the reinstatement phase (P < 0.01). Furthermore, diazepam injection (3 mg/kg) before the methamphetamine priming dose did not have any significant effect on the reinstatement of drug-seeking. Conclusions: This study demonstrated that administration of diazepam during the extinction period was associated with reduced maintenance and reinstatement of methamphetamine-induced CPP, while the single dose of diazepam could not prevent the reinstatement of methamphetamine.

Universal properties of the dynamics of the Covid-19 pandemics

We present evidence for existence of a universal lower bound for the initial growth rate of the epidemic curve of the SARS-CoV-2 coronavirus. This can be used to infer that, on average, an asymptomatic infected individual is infectious during 5.6 plus/minus 0.3 days. We further present evidence of an average time scale of 12 days for halving the number of new cases, or new deaths, during the extinction period of the first phase of the epidemic.

The transition and meaning of the ceremonial ornament with bird-shaped thorn(有刺괿器) from Marisan ancient tombs in Haman region

The Malisan ancient tombs in Haman region are the most important sites, as the center of Allakuk(安羅國), in the study of Gaya. In this study, the ceremonial ornament with bird-shaped thorn(有刺利器) excavated from the Malisan tombs were examined. In the analysis of the ceremonial ornament, It attracts attention to the most distinctive part of the bird-shaped decoration. It is largely classified into the old and the new style. It is set to five types of old style and three types of new style. The old and new style differ in appearance and disappearance. The set pattern is observed to change gradually from the early period to the late period. The duration is divided into five stages from the beginning of the 5th century to the beginning of the 6th century. The scale of the wooden chamber tombs and stone chamber tombs and the main artifacts were examined, and the hierarchy was classified. The ceremonial ornament shows the hierarchical feature that is buried only in the middle grave and above. From the time of the emergence until the extinction period, the position as a superior relics was maintained. The position to be buried is changed. Artifacts what was buried near the body, it changes to the form to be placed on the vice chamber or top of the main in the late period. The ceremonial ornament excavated from the Malisan tombs is confirmed a close connection with the Gimhae region in the 4th century. The bird-shaped decoration on back of the armor excavated from the Daeseongdong No. 2 tomb is very similar to that of the earliest period in the old style of the Malisan s ceremonial ornament. From the previous period, the image of the bird-shaped decoration were identified in various artifacts as an important notion of farming rituals, worship of the sky and sun, and ceremonial rituals. It can be seen that the building group of the Malisan tombs placed the ceremonial ornament that has a symbolic meaning on the grave with a high hierarchy continuously.

4. The radiation of mammals

For two-thirds of their entire history, right through the 135 million years left of the Mesozoic Era, mammals were all small, secretive animals feeding at night on insects, worms, seeds, and plant tubers. Mammals were restricted in size due to their competition with the dinosaurs. But mammalian evolution continued and early examples of placentals and marsupials have been dated to this period. ‘The radiation of mammals’ outlines the end-Cretaceous mass extinction period 65 mya when over 60 per cent of all living species disappeared. It also describes the Tertiary radiation of mammals through changing climates, and the mammalian evolution on the island continents of Australia and South America.

Administration of the glial cell modulator, minocycline, in the nucleus accumbens attenuated the maintenance and reinstatement of morphine-seeking behavior

Relapse to drug use is one of the most difficult clinical problems in treating addiction. Glial activation has been linked with the drug abuse, and the glia modulators such as minocycline can modulate the drug abuse effects. The aim of the present study was to determine whether minocycline could attenuate the maintenance and reinstatement of morphine. Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) for 3 days. Following the acquisition of the CPP, the rats were given daily bilateral intra-NAc injections of either minocycline (1, 5, and 10 μg/0.5 μL) or saline (0.5 μL). The animals were tested for conditioning score 60 min after each injection. To induce the reinstatement, a priming dose of morphine (1 mg/kg) was injected 1 day after the final extinction day. The morphine-induced CPP lasted for 7 days after cessation of morphine treatment. Our data revealed that a priming dose of morphine could reinstate the extinguished morphine-induced CPP. Daily intra-accumbal injection of minocycline during the extinction period blocked the maintenance of morphine CPP and also attenuated the priming-induced reinstatement. Our findings indicated that minocycline could facilitate the extinction and attenuate the reinstatement of morphine. These results provided new evidence that minocycline might be considered as a promising therapeutic agent for the treatment of several symptoms associated with morphine abuse.