Psychedelics are a class of drugs that produce unique subjective effects via agonist actions at the 5-hydroxytryptamine 2A receptor (5-HT 2A ). The 5-HT 2A -mediated head twitch response (HTR) in rodents is used as a reliable proxy for psychedelic drug activity in humans, but existing methods for measuring HTRs require surgery or time-consuming visual scoring. In the present work, we validated a simple noninvasive method for quantitating HTRs using computer-based analysis of experimental video recordings. Male C57BL/6J mice received injections of the 5-HT 2 receptor agonist (±)2,5-dimethoxy-4-iodoamphetamine (DOI; 0.03−3 mg/kg, s.c.) and were placed into cylindrical arenas. High frame rate videos were recorded via cameras mounted above the arenas. Antagonist experiments, which entailed pretreatment with the 5-HT 2A antagonist M100907 (0.01 or 0.1 mg/kg s.c.) prior to DOI (1 mg/kg s.c.), were also recorded. The experimental videos were analyzed for HTRs using a newly developed feature of a commercial software package and compared to visual scoring carried out by trained observers. As expected, DOI produced dose-related increases in HTRs, which were blocked by M100907. Computer scoring was positively correlated with visual scoring, and no statistical difference between the two methods was found. The software captured nearly all visually observed HTRs, false positives induced by other behaviors (e.g., grooming) were rare and easily identified, and results were improved by optimizing lighting conditions. Our findings demonstrate the utility of combining high frame rate video recordings with commercial software analyses to measure HTRs, validating an additional reliable method to study psychedelic-like drug activity in mice.
This paper presents a vision-based, computationally efficient method for simultaneous robot motion estimation and dynamic target tracking while operating in GPS-denied unknown or uncertain environments. While numerous visionbased approaches are able to achieve simultaneous ego-motion estimation along with detection and tracking of moving objects, many of them require performing a bundle adjustment optimization, which involves the estimation of the 3D points observed in the process. One of the main concerns in robotics applications is the computational effort required to sustain extended operation. Considering applications for which the primary interest is highly accurate online navigation rather than mapping, the number of involved variables can be considerably reduced by avoiding the explicit 3D structure reconstruction and consequently save processing time. We take advantage of the light bundle adjustment method, which allows for ego-motion calculation without the need for 3D points online reconstruction, and thus, to significantly reduce computational time compared to bundle adjustment. The proposed method integrates the target tracking problem into the light bundle adjustment framework, yielding a simultaneous ego-motion estimation and tracking process, in which the target is the only explicitly online reconstructed 3D point. Our approach is compared to bundle adjustment with target tracking in terms of accuracy and computational complexity, using simulated aerial scenarios and real-imagery experiments.
Background:
MDPV (3,4-methylenedioxypyrovalerone) is a synthetic stimulant that blocks transmitter uptake at transporters for dopamine and norepinephrine. Less is known about MDPV pharmacokinetics,
especially with respect to brain concentrations of the drug and its metabolites.
Objectives:
The goal of the present study was: 1) to determine brain concentrations of MDPV and its metabolites, 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxy-pyrovalerone (4-OH-3-MeOPV), after administration of MDPV, and 2) to relate brain pharmacokinetic measures to pharmacodynamic endpoints in the same subjects.
Methods:
Male Sprague-Dawley rats (300-400 g) received s.c. MDPV injection (1, 2, or 4 mg/kg) or its saline
vehicle. Groups of rats were decapitated at 40 min and 240 min postinjection. Locomotor behavior was rated
before decapitation, and the core temperature was obtained. Plasma and frontal cortex were analyzed to quantitate MDPV and its metabolites. Striatal samples were analyzed to measure dopamine, serotonin (5-HT), and
their metabolites.
Results:
MDPV displayed brain-to-plasma ratios greater than 1 (range 8.8-12.1), whereas 3,4-catechol-PV and
4-OH-3-MeO-PV showed ratios less than 1 (range 0-0.3). MDPV increased behavioural scores reflective of locomotor stimulation at 40 and 240 min and produced slight hyperthermia at 240 min. MDPV had no effect on
striatal dopamine but produced an increase in the metabolite homovanillic acid (HVA). Brain MDPV concentrations were positively correlated with behavioural scores and striatal HVA but not with other endpoints.
Conclusion:
The behavioural effects of MDPV are related to brain concentrations of the parent drug and not its
metabolites. The modest effects of MDPV on monoamine systems suggest that other non-monoamine mechanisms may contribute to the effects of the drug in vivo.
Synthetic cathinones are a class of new psychoactive substances that display psychomotor stimulant properties, and novel cathinone analogs continue to emerge in illicit drug markets worldwide. The aim of the present study was to characterize the pharmacology of 4-chloro ring-substituted cathinones that are appearing in illicit drug markets, as compared to the effects of 4-methylmethcathinone (mephedrone).Synaptosomes were prepared from rat caudate for dopamine transporter (DAT) assays, or from whole brain minus caudate and cerebellum for norepinephrine transporter (NET) and serotonin transporter (SERT) assays. Findings from transporter uptake inhibition and release assays showed that mephedrone and 4-chloromethcathinone (4-CMC) function as substrates at DAT, NET, and SERT, with similar potency at all three transporters. In contrast, 4-chloro-α-pyrrolidinopropiophenone (4-CαPPP) was an uptake inhibitor at DAT and NET, with similar potency at each site, but had little activity at SERT. 4-Chloroethcathinone (4-CEC) was a low potency uptake inhibitor at DAT and NET but a substrate at SERT. In rats implanted with telemetry transmitters, mephedrone and 4-CMC increased blood pressure, heart rate, and locomotor activity to a similar extent. 4-CEC and 4-CαPPP were less potent at increasing blood pressure and had modest stimulatory effects on heart rate and activity. 4-CMC also transiently decreased temperature at the highest dose tested. All three 4-chloro ring-substituted cathinones are biologically active, but only 4-CMC has potency comparable to mephedrone.Collectively, our findings suggest that 4-CMC and other 4-chloro cathinones may have abuse potential and adverse effects in humans that are analogous to those associated with mephedrone.
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