BACKGROUND AND PURPOSE5-HT6 receptors are abundant in the hippocampus, nucleus accumbens and striatum, supporting their role in learning and memory. Selective 5-HT6 receptor antagonists produce pro-cognitive effects in several learning and memory paradigms while 5-HT6 receptor agonists have been found to enhance and impair memory. EXPERIMENTAL APPROACHThe conditioned emotion response (CER) paradigm was validated in rats. Then we examined the effect of the 5-HT6 receptor antagonist, EMD 386088 (10 mg·kg KEY RESULTSPairing unavoidable foot shocks with a light and tone cue during CER training induced a robust freezing response, providing a quantitative index of contextual memory when the rat was returned to the shock chamber 24 h later. Pretreatment (-20 min pre-training) with scopolamine or MK-801 reduced contextual freezing 24 h after CER training, showing production of memory impairment. Immediate post-training administration of 5-HT6 receptor antagonist, SB-270146, and agonists, EMD 386088 and E-6801, had little effect on CER freezing when given alone, but all significantly reversed scopolamine-and MK-801-induced reduction in freezing. CONCLUSION AND IMPLICATIONSBoth the 5-HT6 receptor agonists and antagonist reversed cholinergic-and glutamatergic-induced deficits in associative learning. These findings support the therapeutic potential of 5-HT6 receptor compounds in the treatment of cognitive dysfunction, such as seen in Alzheimer's disease and schizophrenia.

This study assessed the effects of a fatiguing game simulation (G-Sim) on the balance of collegiate Canadian football players. The purpose of the study was to evaluate postural control as a potential tool for monitoring neuromuscular fatigue (NMF) in collision-based team sports. Fifteen male Canadian football players were recruited (mean±SD: age 21.8±1.6 years, weight 97.6±14.7 kg). Indirect NMF measures (postural sway and countermovement jump (CMJ)) were performed 24 h before (TBase), immediately before (TPre) and after (TPost), and 24 h (T24) and 48 h after (T48) a Canadian football G-Sim. Peak isometric knee extensor torque of a maximal voluntary contraction (MVC) and electrically evoked tetani at 20 Hz (P20) and 80 Hz (P80) were also recorded as direct NMF measures at TBase, TPre, TPost, and T48. At TPost, we observed significant declines in MVC, P20, and the MVC/P80 ratio (-15.3%, -15.7%, and -12.1%, respectively; n=12) along with reductions in CMJ takeoff velocity and peak power (-6.9% and -6.5%, respectively; n=12) and larger area of the center of pressure trajectory (95.2%; n=10) during a 60-s postural sway task. All variables were no longer different than baseline by T48. Acute neuromuscular impairment in this cohort is likely attributable to alterations in excitation-contraction coupling due to structural damage and central activation failure. Congruency between the direct and indirect measures of NMF suggests monitoring postural sway has the potential to identify both neuromuscular and somatosensory alterations induced by acute game-induced fatigue in collision-based team sports players.

Contemporary meta-analyses have generally demonstrated a positive effect of sodium bicarbonate (NaHCO 3) supplementation on exercise performance. However, despite these claims, there is limited data on contrasting individualized and standardized timing of NaHCO 3 ingestion prior to exercise to further enhance performance outcomes. Purpose: To determine whether NaHCO 3 ingestion timing impacts 2,000-m rowing time-trial (TT) performance in elite-level rowers (Senior National team including Olympic/World Championships level) adhering to their own individualized pre-race strategies (e.g. nutrition, warm-up, etc.). Methods: Twenty three (n = 23) rowers across two research centers (using the exact same methods/protocols) completed three trials: NaHCO 3 loading profile at rest to determine the individual's time-to-peak bicarbonate concentration [HCO − 3 ], followed by two randomized 0.3 g•kgBM −1 NaHCO 3 supplementation experimental trials conducted at different time points [consensus timing (CON): TT performed 60 min post-NaHCO 3 ingestion; and individualized peak (IP): TT performed at the rower's individual peak [HCO − 3 ] determined from the profiling trial post-NaHCO 3 ingestion]. Results: There was a significant mean difference of +2.9 [± 0.4 mmol•L −1 HCO − 3 for IP vs. CON (95% CI 2.0 to 3.8 mmol•L −1); p = 0.02; d = 1.08] at pre warm-up, but not immediately prior to the TT (post warm-up). Performance times were significantly different between IP (367.0 ± 10.5 s) vs. CON (369.0 ± 10.3 s); p = 0.007; d = 0.15). Conclusions: The present study demonstrated a small but significant performance effect of an individualized NaHCO 3 ingestion strategy. Similarities after warm-up between pre-TT sHCO − 3 values (CON ∼ + 5.5 mmol•L −1 ; IP ∼ + 6 mmol•L −1), however, would suggest this effect was not a result of any meaningful differences in blood alkalinity.