Kappa Opioid Receptors in Mesolimbic Terminals Mediate Escalation of Cocaine Consumption.

Increases in drug consumption over time, also known as escalation, is a key behavioral component of substance use disorder (SUD) that is related to potential harm to users, such as overdose. Studying escalation also allows researchers to investigate the transition from casual drug use to more SUD-like drug use. Understanding the neurobiological systems that drive this transition will inform therapeutic treatments in the aim to prevent increases in drug use and the development of SUD. The kappa opioid receptor (KOR) system is typically known for its role in negative affect, which is commonly found in SUD as well. Furthermore, the KOR system has also been implicated in drug use and importantly, modulating the negative effects of drug use. However, the specific neuronal subpopulation expressing KOR involved has not been identified. Here, we first demonstrated that pharmacologically inhibiting KOR in the nucleus accumbens core (NAcC), as a whole, blocks cocaine escalation under long-access self-administration conditions. We then demonstrated that KOR expressed on ventral tegmental area (VTA) neurons but not NAcC neurons is sufficient for blocking cocaine escalation by utilizing a novel virally-mediated CRISPR-SaCas9 knock-out of the oprk1 gene. Together, this suggests that activation of KOR on VTA terminals in the NAcC drives the transition to the SUD-like phenotype of escalation of cocaine consumption.

Reference values of blood parameters in beef cattle of different ages and stages of lactation.

Reference (normal) values for 12 blood serum components were determined for 48 Shorthorn cows (2-10 years old) and their 48 calves, 357 crossbred cows (12-14 years old), 36 feedlot bulls and 36 feedlot steers. In addition, hemoglobin, hematocrit, triiodothyronine, thyroxine and cortisol levels were determined for the crossbred cows, and feedlot bulls and steers. Reference values were tabulated according to sex, age and stage of lactation. Serum concentrations of urea, total protein and bilirubin, and serum activity of aspartate aminotransferase and lactate dehydrogenase increased with age (P less than 0.05), while calcium, phosphorus and alkaline phosphatase decreased with age (P less than 0.05) from birth to the age of ten years. The Shorthorn cows had the highest levels of glucose at parturition (P less than 0.05) with decreasing levels during lactation. Creatinine concentration decreased during lactation and increased during postweaning. Both lactate dehydrogenase and aspartate aminotransferase levels increased (P less than 0.05) during lactation. Urea and uric acid were present at higher concentrations in lactating than nonlactating cows (P less than 0.05). The values reported, based on a wide age range and large number of cattle, could serve as clinical guides and a basis for further research.

Blood and serum components and organ weights in steers, bulls and zeranol-implanted bulls.

To investigate certain physiological aspects of the mode of action of zeranol or Ralgro on growth, behavior and carcass quality of young bulls, concentrations of 19 blood components and weights of eight organs were determined. Experimental animals consisted of 36 untreated steers, 36 untreated bulls, 36 bulls implanted with zeranol at 3 mo of age and subsequently at 5, 8 and 10 mo and 36 bulls implanted with zeranol at 6 mo of age and subsequently at 9 and 11 mo. In addition, half of the animals in each group were subjected to moderate pre-slaughter stress (mixing and trucking 160 km); the other half was subjected to minimum pre-slaughter stress (no mixing and 4 km transport). Concentrations of cortisol, urea nitrogen and albumin in serum were higher (P less than .01) and those of glutamic oxaloacetic transaminase (GOT), lactate dehydrogenase (LDH), alkaline phosphatase (AP) and creatinine were lower (P less than .05) in steers than in intact males. Concentrations of GOT, LDH, and creatinine were higher (P less than .05) in implanted than those in control males. Pre-slaughter stress had a significant effect on several traits measured in blood or serum. Thyroid glands were smaller (P less than .01) in steers than in control and implanted males. Testes were smaller (P less than .01) in the zeranol-implanted than in untreated males. Results indicate that zeranol had only a minor effect on the 19 blood components studied, but it did reduce testicle size. Castration had a major impact on several of the blood components. Pre-slaughter management had a significant effect on several blood components.

Review: ethidium fluorescence assays. Part 1. Physicochemical studies.

DNA and RNA can be assayed rapidly and very sensitively by exploiting the enhanced fluorescence of ethidium intercalated into duplex regions. By assaying at different pHs and introducing a heating/cooling cycle, a great many physicochemical aspects of DNA and RNA can be studied avoiding the use of radiolabels, and often giving information not otherwise readily obtainable. Studies are described on duplex DNA which involve measurement of extinction coefficients, cross-linking by chemicals, Cot curve analysis as well as estimation of drug-DNA binding constants. The assays can be adapted to investigate multi-stranded nucleic acid structures. The use of covalently closed circular DNA also allows rapid and extremely sensitive measurements of nicking caused by irradiation or drugs.