A Three-Way Drug Discrimination Study: A Role for DA-Mediated Effects in MDMA's Discriminative Cue Properties

<p>While 3,4-methylenedioxymethamphetamine (MDMA) shares many similarities with amphetamine, previous two choice drug discrimination procedures have shown that substitution between the two substances is inconsistent. Three choice drug discrimination procedures have revealed that MDMA can be discriminated from amphetamine, due to MDMA’s primary influence in releasing 5-HT. Neurochemical evidence had previously suggested that at doses >3.0mg/kg MDMA-induced dopamine (DA) release will increase significantly. In the current study rats were trained to discriminate MDMA from amphetamine and saline. As the dose of MDMA increased beyond the training dose (>1.5mg/kg) MDMA-appropriate responding decreased, while the proportion of amphetamine lever responding increased and eventually surpassed MDMA-appropriate responding at the highest dose (4.5mg/kg). This would indicate an important role for DA mediated influences in MDMA’s discriminative cue properties. Further evidence for this conclusion comes from tests with the D1 antagonist SCH23390 and the D2 antagonist eticlopride which attenuated this effect and also led to a nonsignificant increase in the proportion of saline lever responding. Subsequent tests with the 5-HT2c antagonist RS102221resulted in no significant dose dependent changes, but appeared to reduce MDMA-appropriate responding especially at the training dose. The current findings would suggest that low doses of MDMA are discriminable from amphetamine, however with increasing doses MDMA will be perceived as more “amphetamine-like”. These findings could suggest that at relatively high doses MDMA produces effects that are typically associated with dopamine-releasing drugs, such as high abuse potential.</p>

A Three-Way Drug Discrimination Study: A Role for DA-Mediated Effects in MDMA's Discriminative Cue Properties

<p>While 3,4-methylenedioxymethamphetamine (MDMA) shares many similarities with amphetamine, previous two choice drug discrimination procedures have shown that substitution between the two substances is inconsistent. Three choice drug discrimination procedures have revealed that MDMA can be discriminated from amphetamine, due to MDMA’s primary influence in releasing 5-HT. Neurochemical evidence had previously suggested that at doses >3.0mg/kg MDMA-induced dopamine (DA) release will increase significantly. In the current study rats were trained to discriminate MDMA from amphetamine and saline. As the dose of MDMA increased beyond the training dose (>1.5mg/kg) MDMA-appropriate responding decreased, while the proportion of amphetamine lever responding increased and eventually surpassed MDMA-appropriate responding at the highest dose (4.5mg/kg). This would indicate an important role for DA mediated influences in MDMA’s discriminative cue properties. Further evidence for this conclusion comes from tests with the D1 antagonist SCH23390 and the D2 antagonist eticlopride which attenuated this effect and also led to a nonsignificant increase in the proportion of saline lever responding. Subsequent tests with the 5-HT2c antagonist RS102221resulted in no significant dose dependent changes, but appeared to reduce MDMA-appropriate responding especially at the training dose. The current findings would suggest that low doses of MDMA are discriminable from amphetamine, however with increasing doses MDMA will be perceived as more “amphetamine-like”. These findings could suggest that at relatively high doses MDMA produces effects that are typically associated with dopamine-releasing drugs, such as high abuse potential.</p>

The Minimum Effective Training Dose Required for 1RM Strength in Powerlifters

The aim of this multi-experiment paper was to explore the concept of the minimum effective training dose (METD) required to increase 1-repetition-maximum (1RM) strength in powerlifting (PL) athletes. The METD refers to the least amount of training required to elicit meaningful increases in 1RM strength. A series of five studies utilising mixed methods, were conducted using PL athletes &amp; coaches of all levels in an attempt to better understand the METD for 1RM strength. The studies of this multi-experiment paper are: an interview study with elite PL athletes and highly experienced PL coaches (n = 28), an interview and survey study with PL coaches and PL athletes of all levels (n = 137), two training intervention studies with intermediate-advanced PL athletes (n = 25) and a survey study with competitive PL athletes of different levels (n = 57). PL athletes looking to train with a METD approach can do so by performing ~3–6 working sets of 1–5 repetitions each week, with these sets spread across 1–3 sessions per week per powerlift, using loads above 80% 1RM at a Rate of Perceived Exertion (RPE) of 7.5–9.5 for 6–12 weeks and expect to gain strength. PL athletes who wish to further minimize their time spent training can perform autoregulated single repetition sets at an RPE of 9–9.5 though they should expect that strength gains will be less likely to be meaningful. However, the addition of 2–3 back-off sets at ~80% of the single repetitions load, may produce greater gains over 6 weeks while following a 2-3-1 squat-bench press-deadlift weekly training frequency. When utilizing accessory exercises in the context of METD, PL athletes typically utilize 1–3 accessory exercises per powerlift, at an RPE in the range of 7–9 and utilize a repetition range of ~6–10 repetitions.

5-HT1B receptor agonist attenuates cocaine self-administration after protracted abstinence and relapse in rats

Background: The 5-HT1B receptor (5-HT1BR) agonist, CP94253, enhances cocaine intake during maintenance of self-administration (SA) but attenuates intake after 21 days of forced abstinence in male rats. Aims: We examined whether CP94253 attenuates cocaine intake in female rats after a period of abstinence, and if these attenuating effects persist or revert to enhancing cocaine intake during resumption (i.e. relapse) of daily cocaine SA. Methods: Male and female rats trained to lever press on a fixed ratio 5 schedule of cocaine reinforcement underwent ⩾21 days of forced abstinence. They were then tested for the effects of CP94253 (5.6 mg/kg, SC) or vehicle on cocaine SA. During the test session, rats had 1-h access to the training dose of cocaine (0.75 mg/kg, IV) followed by 1-h access to a lower cocaine dose (0.075 mg/kg, IV). Rats then resumed cocaine SA for 15 days to mimic relapse and were retested as done previously. Subsequently, rats underwent abstinence again (21–60 days) and were tested for CP94253 effects on locomotion and cue reactivity (i.e. responding for light/tone cues previously paired with cocaine infusions). Results: Regardless of sex, CP94253 decreased cocaine intake after abstinence and during resumption of SA and decreased cue reactivity while having no effect on locomotion. Conclusions: CP94253 decreases cocaine intake and cocaine seeking in both males and females even after resumption of cocaine SA. These findings suggest that the inhibitory effects of CP94253 observed after abstinence are long-lasting, and therefore, 5-HT1BR agonists may have clinical efficacy as anti-relapse medications for cocaine use disorders.

Evaluating Exercise Progression in an Australian Cardiac Rehabilitation Program: Should Cardiac Intervention, Age, or Physical Capacity Be Considered?

Progression of prescribed exercise is important to facilitate attainment of optimal physical capacity during cardiac rehabilitation. However, it is not clear how often exercise is progressed or to what extent. This study evaluated whether exercise progression during clinical cardiac rehabilitation was different between cardiovascular treatment, age, or initial physical capacity. The prescribed exercise of sixty patients who completed 12 sessions of outpatient cardiac rehabilitation at a major Australian metropolitan hospital was evaluated. The prescribed aerobic exercise dose was progressed using intensity rather than duration, while repetitions and weight lifted were utilised to progress resistance training dose. Cardiovascular treatment or age did not influence exercise progression, while initial physical capacity and strength did. Aerobic exercise intensity relative to initial physical capacity was progressed from the first session to the last session for those with high (from mean (95%CI) 44.6% (42.2–47.0) to 68.3% (63.5–73.1); p < 0.001) and moderate physical capacity at admission (from 53.0% (50.7–55.3) to 76.3% (71.2–81.4); p < 0.001), but not in those with low physical capacity (from 67.3% (63.7–70.9) to 85.0% (73.7–96.2); p = 0.336). The initial prescription for those with low physical capacity was proportionately higher than for those with high capacity (p < 0.001). Exercise testing should be recommended in guidelines to facilitate appropriate exercise prescription and progression.

Different disc characteristics between young elite skiers with diverse training histories revealed with a novel quantitative magnetic resonance imaging method

Purpose To evaluate if there are differences in thoraco-lumbar disc characteristics between elite skiers and non-athletic controls as well as between different types of elite skiers, with diverse training histories, using a novel quantitative MRI method. Methods The thoraco-lumbar spine of 58 elite skiers (age = 18.2 ± 1.1 years, 30 males) and 26 normally active controls (age = 16.4 ± 0.6 years, 9 males) was examined using T2w-MRI. Disc characteristics were compared quantitatively between groups using histogram and regional image analyses to determine delta peak and T2-values in five sub-regions. Results A statistical difference in the delta peak value was found between skiers and controls (p <0.001), reflecting higher degree of disc degeneration. The histogram analysis also revealed that the type of training determines where and to what extent the changes occur. Alpine skiers displayed lumbar changes, while mogul skiers displayed changes also in the thoracic spine. Alpine skiers with diverse training dose differed in delta peak value (p = 0.005), where skiers with highest training dose displayed less changes. Regional T2-value differences were found in skiers with divergent training histories (p <0.05), reflecting differences in disc degeneration patterns, foremost within the dorsal annulus. Conclusion Differences in quantitative disc characteristics were found not only between elite skiers and non-athletic controls but also between subgroups of elite skiers with diverse training histories. The differences in the disc measures, reflecting tissue degradation, are likely related to type and intensity of the physical training. Future studies are encouraged to explore the relation between disc functionality, training history and pain to establish adequate prevention and rehabilitation programs.

A decision-neuroscientific intervention to improve cognitive recovery after stroke

Functional recovery after stroke is dose-dependent on the amount of rehabilitative training. However, rehabilitative training is subject to motivational hurdles. Decision neuroscience formalizes drivers and dampers of behaviour and provides strategies for tipping motivational trade-offs and behaviour change. Here, we used one such strategy, upfront voluntary choice restriction (‘precommitment’), and tested if it can increase the amount of self-directed rehabilitative training in severely impaired stroke patients. In this randomized controlled study, stroke patients with working-memory deficits (n = 83) were prescribed daily self-directed gamified cognitive training as an add-on to standard therapy during post-acute inpatient neurorehabilitation. Patients allocated to the precommitment intervention could choose to restrict competing options to self-directed training, specifically the possibility to meet visitors. This upfront choice restriction was opted for by all patients in the intervention group and highly effective. Patients in the precommitment group performed the prescribed self-directed gamified cognitive training twice as often as control group patients who were not offered precommitment (on 50% vs. 21% of days, pcorr = .004, d = .87, CI95% = [.31, 1.42]), and, as a consequence, reached a three times higher total training dose (90.21 vs. 33.60 minutes, pcorr = .004, d = .83, CI95% = [.27, 1.38]). And, add-on self-directed cognitive training was associated with stronger improvements in visuospatial and verbal working-memory performance (pcorr =.002, d = .72, and pcorr = .036, d = .62). Our decision-neuroscientific add-on intervention strongly increased the performed amount of an effective cognitive training in severely impaired stroke patients. These results warrant a full clinical trial to directly link decision neuroscientific interventions to clinical outcome.

External, Internal, and Perceived Training Loads and Their Relationships in Youth Basketball Players Across Different Positions

Purpose: To quantify external, internal, and perceived training loads and their relationships in youth basketball players across different playing positions. Methods: Fourteen regional-level youth male players (age: 15.2 [0.3] y) were monitored during team-based training sessions across 10 in-season weeks. The players were monitored with BioHarness-3 devices, to measure external (Impulse Load, in Newtons per second) and internal (summated-heart-rate zones [SHRZ], in arbitrary units [AU]) loads, and with the session rating of perceived exertion (sRPE, in AU) method to quantify perceived training load. Multiple linear mixed models were performed to compare training loads between playing positions (backcourt and frontcourt). Repeated-measures correlations were performed to assess the relationships between the load models, for all players and within playing positions. Results: External load (backcourt: 13,599 [2260] N·s; frontcourt: 14,934 [2173] N·s) and sRPE (backcourt: 345 [132] AU; frontcourt: 505 [158] AU) were higher in the frontcourt (P < .05, effect size: moderate), while SHRZ was similar between positions (backcourt: 239 [45] AU; frontcourt: 247 [43] AU) (P > .05; effect size: trivial). The correlations were as follows: large between the external load and SHRZ (r = .57, P < .001), moderate between SHRZ and sRPE (r = .45, P < .001), and small between the external load and sRPE (r = .26, P = .02). The correlation magnitudes were equivalent for external load–SHRZ (large) and SHRZ–sRPE (moderate) across positions, but different for the external load–sRPE correlation (small in backcourt; moderate in frontcourt). Conclusions: In youth basketball, small–large commonalities were found between the training dose (external load) and players’ responses (internal and perceived loads). Practitioners should carefully manage frontcourt players’ training loads because they accumulate greater external and perceived loads than backcourt players do.

Optimizing training programs for athletic performance: a Monte-Carlo Tree Search variant method

PurposeUsing a variant of the Monte-Carlo Tree Search (MCTS) algorithm, we compute optimal personalized and generic training programs for athletic performance.MethodsWe use a non-linear performance model with population variability for athletes and non-athletes previously used in the literature. Then, we simulate an in-silico test population. For each individual of this population, we compute the performance obtained after implementing several widely used training programs as well as the one obtained by our variant of the MCTS algorithm. Two cases are considered depending on individual parameters being observed and personalized programs being possible or only parameter distributions being available and only generic training programs being implementable.ResultsCompared to widely used training programs, our optimization leads to an increase in performance between 1.1 (95% CI: 0.9 – 1.4) percentage point of the performance obtained with stationary optimal training dose (pp POTD) for athletes and unknown individual characteristics to 10.0 (95% CI: 9.6 – 10.3) pp POTD for nonathletes and known individual characteristics. The value of information when using MCTS optimized training strategies, i.e. the difference between the performance that can be reached with knowledge of individual characteristics and the performance that can be reached without it is 14.7 (95% CI: 12.8 – 16.7) pp POTD for athletes and 3.0 (95% CI: 2.6 – 3.4) pp POTD for non-athletes.