DREADD activation of the lateral orbitofrontal increases cocaine-taking and cocaine-seeking in male and female rats during intermittent access self-administration under risky conditions.

Addiction is a disorder that can be characterized in part as the constant pursuit of a particular substance despite negative consequences. Although the orbitofrontal cortex (OFC) is known to regulate risk-taking more generally and be critical to the development of addiction, its role in regulating drug use under risk-taking conditions is unknown. To address this, we examined drug-taking and drug-seeking in male and female rats under conditions where cocaine infusions were paired with foot shock punishment 50% of the time and combined this paradigm with cFos immunohistochemistry. We found that rats that showed higher levels of drug-taking and drug-seeking prior to punishment showed decreased responding during self-administration sessions under risky conditions and lower levels of c-Fos expression in the lateral but not medial OFC. However, despite these initial differences in responses to infusions paired with foot shocks, all rats showed decreased responding with additional punishment sessions. We then used chemogenetic viral approaches to examine how altering activity of the lateral OFC affects drug-taking and drug-seeking during punished drug use. Although there was no effect of Gi/o DREADD-mediated inhibition of the lateral OFC on these behaviors, Gq DREADD-mediated activation increased drug-taking and drug-seeking when drug use was associated with foot shock 50% of the time. Interestingly, this manipulation had no effect on non-risky self-administration behavior. These results suggest that the involvement of lateral OFC in cocaine use is context-sensitive and influences decision-making based on negative outcomes.

Doping Knowledge, Attitude and Practice of Pharmacists in Dessie, Northeast Ethiopia.

BACKGROUND: Doping includes tampering, possession; trafficking; administration, assisting, encouraging, aiding, conspiring a prohibited substance, and an anti-doping rule violation. Doping in sports is increasing and diversifying involving physiological, mechanical, and pharmacological techniques and becoming a serious public health problem. Pharmacy professionals have a vital role in the fight against doping. This study assessed the knowledge, attitude, and practice of pharmacists on the use of doping agents by sportsmen and women. METHODS: A community-based cross-sectional descriptive study was done targeting community pharmacists of Dessie city, Northeast Ethiopia. Structured questionnaires were distributed and collected between April and March of 2018. Data were analyzed using SPSS version 20.0. Linear regression was used and the level of statistical significance was set at a p-value <0.05. RESULTS: Of the 61 pharmacy professionals who participated in the study, 46 (75.4%) were males and 15 (24.6%) were females. Only 25 (41.0%) and 13 (21.3%) of the respondents said they watch and play sport regularly, respectively. The majority of the participants, 50 (82%), supported the prohibition of performance-enhancing drugs in sport. The majority of the respondents, 55.7%, agree that pharmacists are a potential source of doping agents. Only 27.9% of them mentioned World Anti-doping Agency (WADA) as the source of information about doping agents. Regarding identifying the WADA status of 13 agents, the average score out of 13 was 4.95, while 80.3% of them scored less than or equal to seven. Factors associated with knowledge of participants were being male (ß = 4.48, p= 0.02) and regularly watching sport (ß = 2.64, p= 0.01). CONCLUSION: Even though the pharmacists' low knowledge score revealed that they need further specialized training on doping and anti-doping, majority of them support banning doping substances from sport. Pharmacy curriculum developers should consider incorporating specific topics or courses about doping agents.