Abuse of substances or methods to enhance the performance is becoming very common in the sports, which often destroys the spirit of competition. The regulatory bodies for sports have reported rates ranging from 5% to 31% for the use of performance-enhancing substances among athletes. Athletes can have serious injuries and morbidities, leading to poor health with the use of such substances. Commonly abused agents in sports include anabolic-androgenic steroids and its analogs, blood, erythropoietin, growth hormone and its derivatives, nutritional supplements, creatine, amphetamines, beta-hydroxy-beta-methylbutyrate (HMB), stimulants, and analgesics. Health-care professionals need to be careful while prescribing medicines to sportspersons. Knowledge of exercise physiology, pharmacology of the commonly used agents for sports-related injuries, and agents used for doping could help the sportspersons and health-care professionals to avoid the embarrassment arising because of misuse of these agents. Sports pharmacology includes study of the various aspects of the drug use and abuse in sports and treatment of sports-related injuries. Focusing on sports pharmacology in the medical curriculum can help the upcoming health-care professionals to support the sportspersons to improve the quality of their life by using various drugs and other substances within the standardized limits and avoid embarrassment of doping.

There is little information regarding effects of fasting on feeding behavior and hypothalamic physiology in young Japanese quail. The aim was thus to measure food intake and hypothalamic mRNA in response to fasting and refeeding. Five d-old quail ate little during the dark cycle. Food intake was greatest during the first 2 h of the light cycle. Six day-old quail fasted for 6 h ate the most during the first 15 min of refeeding. In 7 d-old quail, 3 h of fasting up-regulated hypothalamic neuropeptide Y (NPY), NPY receptor sub-type 2 (NPYR2), agouti-related peptide (AgRP), orexin receptor 2 (ORXR2), melanocortin receptors 3 and 4 (MC3R and MC4R, respectively), and neuropeptide S (NPS) and decreased corticotropin-releasing factor receptor sub-type 1 (CRFR1) mRNA. Quail fasted for 3 h and refed for 1 h had greater NPY, AgRP, POMC, and MC3R but less CRFR1 mRNA than fed quail. Quail fasted for 6 h expressed more NPY, NPYR1, NPYR2, and MC3R and less ORXR2, prolactin releasing peptide (PrRP), cocaine- and amphetamine-regulated transcript (CART), and calcitonin (CAL) mRNA than fed quail. Quail fasted for 6 h and refed for 1 h expressed more NPY, NPYR1, NPYR2, AgRP, MC3R, MC4R, and NPS and less galanin, ORXR2, PrRP, CART, and CAL mRNA than fed birds. Hence, fasting induced changes in hypothalamic mRNA, with the largest changes occurring in genes associated with NPY and melanocortin signaling. Most genes remained elevated or downregulated after refeeding, suggesting that there was a time lag for transcription to respond to compensatory feeding.

The trace amine associated receptor 1 (TAAR1) is a G-protein coupled receptor expressed in the monoaminergic regions of the brain, and represents a potential novel therapeutic target for the treatment of neurological disorders. While selective agonists for TAAR1 have been successfully identified, only one high affinity TAAR1 antagonist has been described thus far. We previously identified four potential low potency TAAR1 antagonists through an in silico screen on a TAAR1 homology model. One of the identified antagonists (compound 22) was predicted to have favorable physicochemical properties, which would allow the drug to cross the blood brain barrier. In vivo studies were therefore carried out and showed that compound 22 potentiates amphetamine- and cocaine-mediated locomotor activity. Furthermore, electrophysiology experiments demonstrated that compound 22 increased firing of dopamine neurons similar to EPPTB, the only known TAAR1 antagonist. In order to assess whether the effects of compound 22 were mediated through TAAR1, experiments were carried out on TAAR1-KO mice. The results showed that compound 22 is able to enhance amphetamine- and cocaine-mediated locomotor activity, even in TAAR1-KO mice, suggesting that the in vivo effects of this compound are not mediated by TAAR1. In collaboration with Psychoactive Drug Screening Program, we attempted to determine the targets for compound 22. Psychoactive Drug Screening Program (PDSP) results suggested several potential targets for compound 22 including, the dopamine, norepinephrine and serotonin transporters; as well as sigma 1 and 2 receptors. Our follow-up studies using heterologous cell systems showed that the dopamine transporter is not a target of compound 22. Therefore, the biological target of compound 22 mediating its psychoactive effects still remains unknown.

The giant grouper Epinephelus lanceolatus is an ecologically vulnerable species with high market demand. However, efforts to improve larval husbandry are hindered by a lack of knowledge surrounding larval developmental physiology. To address this shortfall, a transcriptomic approach was applied to larvae between 1 and 14 days post hatch (dph) to characterise the molecular ontogenesis of genes that influence appetite and digestion. Appetite regulating factors were detected from 1 dph, including neuropeptide Y, nesfatin-1, cocaine and amphetamine regulated transcript, cholecystokinin and pituitary adenylate cyclase activating peptide and the expression level of several genes changed sharply with the onset of exogenous feeding. The level of expression for proteases, chitinases, lipases and amylases typically followed one of two expression patterns, a general increase as development progressed, or an inverted U-shape with maximal expression at c. 6 dph. Similarly, the tendency among both expression patterns was for the level of expression to increase around the time of mouth-opening. There was also evidence to suggest the presence of putative isoforms for several digestion-related genes. We have provided an insight into appetite-regulation and digestive processes in groupers during early larval development and have developed a transcriptomic database that will aid future efforts to rear this species in an aquaculture setting.

β-Phenylethylamine (β-PEA) is a trace amine with chemical proximity to biogenic amines and amphetamines. It is an endogenous agonist of trace amine-associated receptors (TAARs) that acts as a neuromodulator of classic neurotransmitters in the central nervous system. At high concentrations, β-PEA contracts smooth muscle, and a role for TAARs in these responses has been postulated. The high dietary intake of trace amines has been associated with such symptoms as hypertension and migraine, especially after the intake of foods containing such compounds. In gastrointestinal tissues, TAAR expression was reported, although the effect of β-PEA on gastric contractile behavior is unknown. Here, isolated strips that were obtained from the rat gastric fundus were stimulated with high micromolar concentrations of β-PEA. Under resting tonus, β-PEA induced contractions. In contrast, when the strips were previously contracted with KCl, a relaxant response to β-PEA was observed. The contractile effect of β-PEA was inhibited by 5-hydroxytryptamine (5-HT) receptor antagonists (i.e., cyproheptadine and ketanserin) but not by the TAAR1 antagonist EPPTB. In gastric fundus strips that were previously contracted with 80 mM KCl, the relaxant effect of β-PEA intensified in the presence of 5-HT receptor antagonists, which was inhibited by EPPTB and the adenylyl cyclase inhibitor MDL-12,330A. The guanylyl cyclase inhibitor ODQ did not alter the relaxant effects of β-PEA. In conclusion, β-PEA exerted dual contractile and relaxant effects on rat gastric fundus. The contractile effect appeared to involve the recruitment of 5-HT receptors, and the relaxant effect of β-PEA on KCl-elicited contractions likely involved TAAR1 . This article is protected by copyright. All rights reserved.

Increasing preclinical evidence demonstrates that dopamine D3 receptor (D3R) antagonists are a potential option for the treatment of drug addiction. The reinstatement of the addiction can be triggered by environmental stimuli that acquire motivational salience through repeated associations with the drug's effects. YQA14 is a novel D3R antagonist that has exhibited pharmacotherapeutic efficacy in reducing cocaine and amphetamine reward and relapse to drug seeking in mice. In this study we investigated the effects of YQA14 on morphine-induced context-specific locomotor sensitization in mice. We showed that repeated injection of YQA14 (6.25-25 mg/kg every day ip) prior to morphine (10 mg/kg every day sc) not only inhibited the acquisition, but also significantly attenuated the expression of morphine-induced locomotor sensitization. Furthermore, in the expression phase, one single injection of YQA14 (6.25-25 mg/kg, ip) dose-dependently inhibited the expression of morphine-induced behavioral sensitization. Moreover, YQA14 inhibited the expression of morphine-induced behavioral sensitization in wild mice (WT), but not in D3R knockout (D3R-/-) mice in the expression phase. In addition, D3R-/- mice also displayed the reduction in the expression phase compared with WT mice. In summary, this study demonstrates that blockade or knockout of the D3R inhibits morphine-induced behavior sensitization, suggesting that D3R plays an important role in the pathogenesis and etiology of morphine addiction, and it might be a potential target for clinical management of opioid addiction.

A new drug trafficking trend has been observed in the last years by the introduction in the black market of new psychoactive substances (NPS) in order to difficult competent authority controls. In this study, ion mobility spectrometry (IMS) and high-resolution mass-spectrometry (HRMS) were proposed as vanguard and rearguard methodologies for the rapid identification of the last generation of NPS in seizures. The combined use of IMS and HRMS has been evaluated through the analysis of 24 NPS seized from 2016 to 2018 in Valencia (Spain) to demonstrate the utility of this approach. The characteristic reduced mobility (K0) values for seized NPS were determined and mass-mobility relationships were proposed and evaluated for the main NPS families: amphetamine and cathinone derivatives, and synthetic cannabinoids. IMS did not allow a unequivocal identification by itself; so, HRMS analysis was employed as rearguard confirmation methodology for the right identification of NPS. Thus, the combined use of IMS and HRMS can be considered as promising alternative for the rapid screening and identification of NPS in seizures.

This case report centres on the post-mortem distribution of the synthetic cannabinoid MDMB-CHMICA and its metabolites in the case of a 27-year-old man found dead after falling from the 24th floor of a high-rise building. Toxicological analysis of post-mortem samples confirmed, besides consumption of the synthetic cannabinoids MDMB-CHMICA (1.7 ng/mL femoral blood) and EG-018, the abuse of THC (9.3 ng/mL femoral blood), amphetamine (1050 ng/mL femoral blood), MDMA (275 ng/mL femoral blood), and cocaine. Regarding EG-018 and cocaine, only traces were detected in heart blood as well as in the brain (EG-018) and urine (cocaine), respectively, which is why no quantification was conducted in the femoral blood sample. It was concluded from femoral blood analysis that, at the time of death, the man was under the influence of the synthetic cannabinoid MDMB-CHMICA, THC, amphetamine and MDMA. Comprehensive screenings of all post-mortem specimens were conducted to elucidate the post-mortem distribution of MDMB-CHMICA and its metabolites. The MDMB-CHMICA concentrations ranged between 0.01 ng/mL (urine) and 5.5 ng/g (brain). Comparably low concentrations were detected in cardiac and femoral blood (2.1 ng/mL and 1.7 ng/mL, respectively) as well as in the psoas major muscle (1.2 ng/g). Higher concentrations were found in the lung (2.6 ng/g), liver (2.6 ng/g), and kidney (3.8 ng/g). Gastric content yielded a MDMB-CHMICA concentration of 2.4 ng/g (1.1 μg absolute). Screening for MDMB-CHMICA metabolites resulted in the detection of mainly monohydroxylated metabolites in the blood, kidney, and liver specimens. Results indicated that monohydroxylated metabolites of MDMB-CHMICA are appropriate target analytes for detecting MDMB-CHMICA intake.

In case of drug-facilitated sexual assault (DFSA), the evidence is frequently anecdotal, with few investigations based on scientific evidences being carried out and thus most cases are diagnosed as an acute drug or alcohol intoxication. The reason may lay in the lack of specific knowledge by the victim on the possibility to retrospectively study the allegedly events and to the absence of standardized and shared protocols among health, forensic and police subjects. On this basis, in 2015 the Unit of Forensic Toxicology of University of Florence and the Sexual Assaults Centre in Hospital Careggi have fixed a common protocol to be applied in case of DFSA. The purpose of the study was to describe the results of the application of the shared protocol for toxicological findings among women seeking health care after sexual assault, and to assess the relationship with so-called proactive DFSA drugs. We conducted a study on female patients above 18 years of age consulting the Sexual Assault Centre between 2010 and July 2018. Among the 256 patients included, 37.1% was positive at least for a substance. Alcohol was the most detected substance (57 cases), followed by Cannabis (19 cases), cocaine (15 cases) and opiates/methadone (heroine: 5; morphine:1; methadone: 6); benzodiazepines and amphetamine were found in 13 and in 2 cases, respectively. Only case of gamma-hydroxybutyrate (GHB) consumption was observed while new psychoactive substances were not detected. Among the patients suspecting proactive DFSA, sedative drug findings, not explained by voluntary intake, were encountered.