Self-administration by female rats of low doses of nicotine alone vs. nicotine in tobacco smoke extract.

BACKGROUND: Nicotine has reinforcing effects, but there are thousands of other compounds in tobacco, some of which might interact with nicotine reinforcement. AIMS: This rat study was conducted to determine if nicotine self-administration is altered by co-administration of the complex mixture of compounds in tobacco smoke extract (TSE). METHODS: Female Sprague-Dawley rats were tested for self-administration of low doses of nicotine (3 or 10 µg/kg/infusion) at three different rates of reinforcement (FR1, FR3 and FR5) over three weeks either alone or together with the complex mixture of tobacco smoke extract (TSE). RESULTS: Rats self-administering 3 µg/kg/infusion of nicotine alone showed a rapid initiation on an FR1 schedule, but declined with FR5. Rats self-administering nicotine in TSE acquired self-administration more slowly, but increased responding over the course of the study. With 10 µg/kg/infusion rats self-administered significantly more nicotine alone than rats self-administering the same nicotine dose in TSE. Rats self-administering nicotine alone took significantly more infusions with the 10 than the 3 µg/kg/infusion dose, whereas rats self-administering nicotine in TSE did not. Nicotine in TSE led to a significantly greater locomotor hyperactivity at a dose of 0.1 mg/kg compared to rats that received nicotine alone. Rats self-administering nicotine alone had significantly more responding on the active vs. inactive lever, but rats self-administering the same nicotine doses in TSE did not. CONCLUSIONS: Self-administration of nicotine in a purer form appears to be more clearly discriminated and dose-related than nicotine self-administered in the complex mixture of TSE.

Dextromethorphan and bupropion reduces high level remifentanil self-administration in rats.

Opiate addiction has risen substantially during the past decade. New treatments to combat opiate addiction are sorely needed. The current study was conducted to determine the acute individual and interactive effects of bupropion and dextromethorphan in a rat model of opiate self-administration using the short-acting synthetic opioid remifentanil. Both of these drugs have been found to reduce self-administration of nicotine. Bupropion and dextromethorphan and their combination had differential effects depending on whether the rats showed higher or lower baseline remifentanil self-administration. The rats with higher initial remifentanil self-administration showed a significant decrease in remifentanil self-administration with bupropion or dextromethorphan treatment, compared to the vehicle control condition. This decrease in self-remifentanil administration was most pronounced when combination of the higher doses of bupropion and dextromethorphan were administered. In contrast, the rats with lower baseline remifentanil self-administration showed the opposite effect of drug treatment with an increase in remifentanil self-administration with bupropion treatment compared to the vehicle control condition. Dextromethorphan had no significant effect inthis group. This study shows that combination bupropion and dextromethorphan affects remifentanil self-administration in a complex fashion with differential effects on low and high baseline responders. In subjects with high baseline remifentanil self-administration, bupropion and dextromethorphan treatment significantly reduced self-administration, whereas in subjects with low baseline remifentanil self-administration, bupropion increased remifentanil self-administration and dextromethorphan had no discernible effect. This finding suggests that combination bupropion-dextromethorphan should be tested in humans, with a focus on treating people with high-level opiate use.

Amitifadine, a triple reuptake inhibitor, reduces self-administration of the opiate remifentanil in rats.

RATIONALE: A variety of neural systems are involved in drug addiction, and some of these systems are shared across different addictive drugs. We have found several different types of drug treatments that successfully reduce nicotine self-administration. OBJECTIVES: The current set of studies is the first in a series to determine if drug treatments that have been found to significantly reduce nicotine self-administration would reduce opiate self-administration. METHODS: Amitifadine, a triple reuptake inhibitor of dopamine, norepinephrine, and serotonin, was assessed in female Sprague-Dawley rats to determine whether it significantly reduces remifentanil self-administration with either acute or chronic treatment. RESULTS: Acutely, amitifadine doses of 5, 10, and 20 mg/kg each significantly reduced remifentanil self-administration. In a chronic study, repeated treatment with 10 mg/kg of amitifadine continued to reduce remifentanil self-administration, even after the cessation of treatment. However, amitifadine was not found to attenuate the rise in remifentanil self-administration with continued access. This study and our earlier one showed that the 10 mg/kg amitifadine dose did not significantly affect food motivated responding. Amitifadine did not attenuate remifentanil-induced antinociception as measured on the hot plate test but extended and maintained antinociceptive effects. CONCLUSIONS: These studies show the promise of amitifadine as a treatment for countering opiate self-administration for adjunctive use with opioids for analgesia. Further studies are needed to determine the possible efficacy of amitifadine for combating opiate addiction or preventing it in humans during adjunctive use with opioids for chronic pain.

Development of a Video Recording and Review Process for Trauma Resuscitation Quality and Education.

Video review for quality and education purposes has been a valued tool for decades. However, the use of this process dropped significantly after the development of the Health Insurance Portability and Accountability Act in the 1990s. Video review was recently reestablished at our institution. By working with our institutional legal counsel and risk management team, we have been able to create a video review process that complies with legal requirements. Literature on this subject has not described the process of obtaining video recordings. We aimed to review the process of obtaining high quality recordings in a secure manner. We hope that in the future, the data collected through our multidisciplinary review process will be helpful in improving quality of care for injured patients and providing coaching and feedback to learners, as well as improving our trauma education curriculum.

A Multistep Approach to Address Clinican Knowledge, Attitudes, and Behavior Around Opioid Prescribing.

INTRODUCTION: The Wisconsin Prescription Drug Monitoring Program (PDMP) was implemented in 2013 to reduce the misuse, abuse, and diversion of controlled substance prescriptions. OBJECTIVE: To evaluate provider knowledge, attitudes, and behaviors regarding the Wisconsin PDMP before and after study interventions. METHODS: An initial survey of clinicians, a focus group, pre- and posttests for an educational session, and a 3-month follow-up survey were utilized. RESULTS: Initial survey participants described PDMP use. Focus group themes included system, hospital, clinician, and patient factors. Educational session pre- and posttests showed an increase in provider knowledge. Follow-up surveys demonstrated practice change among providers. CONCLUSION: This study can be useful for health care organizations, state PDMPs, and prevention organizations in tailoring messaging to clinicians around safe prescribing and PDMP use.

Impact of a chronic pain management pathway on opioid administration and prescribing in an Emergency Department.

CONTEXT: Prescription opioid abuse and misuse is a significant public health crisis. In 2012, an opioid prescribing pathway for patients with chronic pain presenting to the Emergency Department (ED) was implemented. The objective of this study is to determine the impact of the pathway for administration of opioids in the ED as well as the prescribing of opioids for home use after discharge. METHODS: Retrospective pre- and post-intervention time series study of consecutive patients presenting to the ED with acute and chronic pain complaints before and after implementation of the pathway. For the purposes of this study, we included patients with chronic abdominal or back pain - defined as pain present for greater than three months - and acute pain as acute long bone fracture. RESULTS: Before pathway implementation, there was no statistically significant difference in the mean morphine equivalent (MEQ) dose administered for chronic or acute pain patients. After pathway implementation, there was a decrease in IV/IM morphine administered to patients with chronic pain (p = .0200) but not to patients with acute pain (p = .0820). Overall, MEQs administered did not change in either group. In the acute pain group, no significant differences were found in the number of patients who received opioid prescriptions upon discharge (p = .7749). However, in the chronic pain group, the number of patients who received opioid prescriptions upon discharge decreased with statistical significance (p = .0017). CONCLUSIONS: After the implementation of a chronic pain management pathway in an ED, there is a decrease noted in opioids administered to patients with chronic pain both in the ED and prescriptions on discharge. In patients presenting with acute pain, there was no change in administration or prescription of opioids.