PRENATAL EXPOSURE TO MODAFINIL ALTERS LOCOMOTOR BEHAVIOUR AND LEUCOCYTE PHAGOCYTOSIS IN MICE

Background: Modafinil is a psychostimulant drug prescribed mainly for treatment of narcolepsy but is used as a “smart drug” by wide populations to increase wakefulness, concentration and overall mental performance. The aim of this study was to assess potential developmental toxicity of modafinil. Materials and methods: Pregnant female mice were given either saline or modafinil (50 mg/kg orally) from gestational day (GD) 3 to GD 10 and then a challenge dose on the GD 17. The male offspring were treated analogously at the age of 10 weeks. Changes in the spontaneous locomotor/exploratory behaviour and anxiogenic profile in the open-field test were assessed in naïve animals, after an acute and 8th modafinil dose and the challenge dose following a 7-day wash-out period. One month after completion of the behavioural study, the leukocyte phagocytosis was examined by zymosan induced and luminol-aided chemiluminiscence assay in vitro. Results: The most important finding of this study was the immunosuppressing effect on leukocyte activity, hypolocomotion and increased behavioural response to modafinil-induced psychostimulation caused by prenatal exposure to the same drug. We did not detect significantly altered anxiety-related behaviour in any group disregarding the pre- and postnatal treatments. Conclusion: This is the first evidence of developmental toxicity of modafinil which needs to be taken into account as a potential risk factor when modafinil is administered to women who may become or are pregnant

Pharmacodynamics of cannabinoids

“Pharmacodynamics of cannabinoids “(i.e. a set of biological effects elicited in the living organism by interaction with its biochemical and biophysical functions up to the cellular level) is studied for a long time during both, physiological and pathological conditions. Cannabinoids received their names according to their natural occurrence as constituents of Cannabis sativa L. (marijuana).&nbsp

Sex differences in the reinstatement of methamphetamine seeking after forced abstinence in Sprague-Dawley rats

Preventing relapse to drug abuse is one of the struggles faced by clinicians in order to treat patients with substance use disorders (DSM-5). There is a large body of clinical evidence suggesting differential characteristics of the disorder in men and women which is in line with preclinical findings as well. The aim of this study was to assess differences in relapse-like behavior in methamphetamine (METH) seeking after a period of forced abstinence which simulates the real clinical situation very well. Findings from such study might add new insights in gender differences in relapse mechanisms to previous studies, which employ a classical drug or cue-induced reinstatement procedure following the extinction training.Adult male and female Sprague-Dawley rats were used in IV self-administration procedure conducted in operant boxes using nose-poke operandi (Coulborn Instruments, USA). Active nose-poke resulted in activation of the infusion pump to deliver one intravenous infusion of METH (0.08 mg/kg). After baseline drug intake was established (maintenance phase), a period of forced abstinence was initiated and rats were kept singly in their home-cages for 14 days. Finally, one reinstatement session in operant boxes was conducted. Females were found to self-administer significantly lower dose of METH. The relapse rate was assessed as a number of active nose-pokes during the reinstatement session, expressed as a percentage of active nose-poking during the maintenance phase. Females displayed approximately 300 % of active nose-pokes compared to 48 % in males. This indicates higher vulnerability to relapse of METH seeking behavior in female rats. This effect was detected in all females, independently of current phase of their estrous cycle. Therefore, this paradigm using operant drug self-administration and reinstatement of drug-seeking after forced abstinence model can be used for preclinical screening for potential new anti-relapse medications specific for women

Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of α-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study

This thesis investigates the economic viability of a grid connected PV system integrated with battery storage in a multifamily home in Sweden. In addition, a fleet of electric cars is added to the system and its economic feasibility is analyzed. The analysis is further classified based on the roof area available for PV installation, wherein system 1 considers nearly the entire roof area of 908 m2 and system 2 is assumed to have less than half the roof area of 360 m2 for PV installation. To help with the assessment, five scenarios are created; where scenario one represents a baseline Swedish cooperative without PV, scenario two includes a PV system; scenario three incorporates battery storage; four considers an electric vehicle fleet embedded into the system and scenario five has a fleet of gasoline cars. These scenarios are applied to the two systems and their results compared. To address the question of this thesis both scenarios 2 and 3 are simulated in System Advisor Model (SAM) and scenario 4 is modeled in Matlab. The outputs are exported to Excel in order to obtain the Net Present Value (NPV), which is the economic indicator for this assessment. In none of the tested scenarios the NPVs’ are positive and the best result is observed in a PV system installed with battery storage in a roof area of 360 m2, which has a NPV of -82,000 SEK. A sensitivity analysis is done to assess the changes in NPV by varying the input parameters. It is concluded that battery storage is not yet economically viable in a Swedish multifamily house

Late-stage alpha-synuclein accumulation in TNWT-61 mouse model of Parkinson's disease detected by diffusion kurtosis imaging

Diffusion kurtosis imaging (DKI) by measuring non-Gaussian diffusion allows the accurate estimation of the distribution of water molecule displacement and may correctly characterize microstructural brain changes caused by neurodegeneration. The aim of the present study was to evaluate the ability of DKI to detect changes induced by α-synuclein (α-Syn) accumulation in both gray matter (GM) and white matter (WM) in α-Syn overexpressing transgenic mice (TNWT-61). The study provides evidence of an association between the amount of α-Syn and the magnitude of DKI metric changes in the ROIs, with the potential of improving the clinical diagnosis of PD