Preparation of biodegradable microspheres and matrix devices containing naltrexone

In this study, the use of biodegradable polymers for microencapsulation of naltrexone using solvent evaporation technique is investigated. The use of naltrexone microspheres for the preparation of matrix devices is also studied. For this purpose, poly(L-lactide) (PLA) microspheres containing naltrexone prepared by solvent evaporation technique were compressed at temperatures above the Tg of the polymer. The effect of different process parameters, such as drug/polymer ratio and stirring rate during preparation of microspheres, on the morphology, size distribution, and in vitro drug release of microspheres was studied. As expected, stirring rate influenced particle size distribution of microspheres and hence drug release profiles. By increasing the stirring speed from 400 to 1200 rpm, the mean diameter of microspheres decreased from 251 μm to 104 μm. The drug release rate from smaller microspheres was faster than from larger microspheres. However, drug release from microspheres with low drug content (20% wt/wt) was not affected by the particle size of microspheres. Increasing the drug content of microspheres from 20% to 50% wt/wt led to significantly faster drug release from microspheres. It was also shown that drug release from matrix devices prepared by compression of naltrexone microspheres is much slower than that of microspheres. No burst release was observed with matrix devices. Applying higher compression force, when compressing microspheres to produce tablets, resulted in lower drug release from matrix devices. The results suggest that by regulating different variables, desired release profiles of naltrexone can be achieved using a PLA microparticulate system or matrix devices

Estradiol modulates effort-based decision making in female rats

Disorders of the dopamine system, such as schizophrenia or stimulant addiction, are associated with impairments in different forms of cost/benefit decision-making. The neural circuitry (i.e. amygdala, prefrontal cortex, nucleus accumbens) underlying these functions all receive dopamine input, which is thought to play a central role in mediating cost/benefit decisions. Estradiol modulates dopamine activity, and estrogen receptors (ERs) are found within this neurocircuitry, suggesting that decision-making may be influenced by estradiol. The present study examined the contribution of estradiol and selective ERα and β agonists on cost/benefit decision-making in adult female Long-Evans rats. An effort-discounting task was utilized, where rats could either emit a single response on a low-reward lever to receive two pellets, or make 2, 5, 10, or 20 responses on a high-reward lever to obtain four pellets. Ovariectomy increased choice on the high-reward lever, while replacement with high (10 μg), but not low (0.3 μg), levels of estradiol benzoate reduced choice on the high-reward lever. Interestingly, both an ERα agonist (PPT) and an ERβ agonist (DPN) increased choice on the high-reward lever when administered independently, but when these two agonists were combined, a decrease in choice for the high-reward lever was observed. The effects of estradiol, PPT, and DPN were more pronounced 24 hr post-administration, suggesting that these effects may be genomic in nature. Together, these results demonstrate that estradiol modulates cost/benefit decision making in females, whereby concomitant activation of ERα and β receptors shifts decision criteria and reduces preference for larger, yet more costly rewards.Arts, Faculty ofPsychology, Department ofNon UBCUnreviewedFacultyResearche