Effects of daily morphine treatment on impulsivity in rats responding under an adjusting stop-signal reaction time task.

Opioids can enhance delay discounting and premature responding under attentional tasks that might reflect increased impulsivity; although it is not clear whether repeated opioid administration alters behavioral inhibition. Effects of morphine and amphetamine were determined before, during, and after daily morphine administration in rats responding under a stop-signal reaction time task, measuring behavioral inhibition and motor impulsivity. Rats (n=5) completed a two-response sequence to earn food. Occasionally, a tone (stop signal) was presented signifying that food would only be presented if the second response was withheld. Responding after the stop signal measured inhibition, and responding before the start of the trial (premature) measured motor impulsivity. Before daily treatment, morphine (0.32-17.8 mg/kg, intraperitoneally) decreased premature responding but did not increase responding on stop trials, whereas amphetamine (0.1-3.2 mg/kg, intraperitoneally) increased premature responding. Daily morphine administration (3.2 mg/kg/day) enhanced its effects on premature responding but did not impact other effects. Daily morphine treatment diminished the effects of amphetamine on premature and timeout responding. Repeated morphine treatment increased motor impulsivity but did not enhance behavioral inhibition. These data add to studies elucidating the relationship between impulsivity and opioid treatment and suggest that opioids differentially impact impulsive behaviors.

Tissue engineering of the gastrointestinal tract: the historic path to translation.

The gastrointestinal (GI) tract is imperative for multiple functions including digestion, nutrient absorption, and timely waste disposal. The central feature of the gut is peristalsis, intestinal motility, which facilitates all of its functions. Disruptions in GI motility lead to sub-optimal GI function, resulting in a lower quality of life in many functional GI disorders. Over the last two decades, tissue engineering research directed towards the intestine has progressed rapidly due to advances in cell and stem-cell biology, integrative physiology, bioengineering and biomaterials. Newer biomedical tools (including optical tools, machine learning, and nuanced regenerative engineering approaches) have expanded our understanding of the complex cellular communication within the GI tract that lead to its orchestrated physiological function. Bioengineering therefore can be utilized towards several translational aspects: (i) regenerative medicine to remedy/restore GI physiological function; (ii) in vitro model building to mimic the complex physiology for drug and pharmacology testing; (iii) tool development to continue to unravel multi-cell communication networks to integrate cell and organ-level physiology. Despite the significant strides made historically in GI tissue engineering, fundamental challenges remain including the quest for identifying autologous human cell sources, enhanced scaffolding biomaterials to increase biocompatibility while matching viscoelastic properties of the underlying tissue, and overall biomanufacturing. This review provides historic perspectives for how bioengineering has advanced over time, highlights newer advances in bioengineering strategies, and provides a realistic perspective on the path to translation.