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Treating impulsivity for cocaine and food in female and male rats by repurposing therapeutics
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Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
Treating impulsivity for cocaine and food in female and male rats by repurposing therapeutics John R. Smethells ∗ , Marilyn E. Carroll University of Minnesota, St. Paul, MN, United States Aims: The ability to engage in recreation drug use requires one to forgo drug use until an appropriate time and place. For instance, many problem users are prone to consume drugs throughout the day, including at work. Treating such compulsions is an important component in treating individuals with drug abuse problems. Methods: The present research modeled impulsive choice for cocaine and food in rats. Specifically female and male rats were given a choice between a larger-later and smaller-sooner alternative. In some conditions, choices were between amounts of food (1 or 3 food pellets) and in others, doses of cocaine (.3 mg/kg or .9 mg/kg infusions of cocaine). In both conditions, once preference for the large alternative was established, delays to the large alternative were introduced and increased each session in ascending order (7.5, 15, 30, 60 sec). Following establishment of a delay gradient (large preference decreased across delay), rats were treated with Progesterone (.05 mg/kg), Atomoxetine (1.5 mg/kg) or together as a combination treatment to determine how they altered impulsivity for food and cocaine. Results: Rats’ preference for the large alternative decreased with increases in large-alternative delay to form a delay gradient. When choosing between doses of cocaine, treatment with Atomoxetine and Progesterone decreased impulsivity (increased large alternative preference relative to baseline) compared to vehicle control in female rats. However, when choosing between amounts of food, neither treatment altered impulsive choice compared to baseline. Conclusions: The initial findings suggest that both Progesterone and Atomoxetine reduce impulsivity for cocaine, but not impulsivity for food. A mechanism thought to the effect is that these treatments reduce the reinforcing efficacy of cocaine; follow-up studies employing a progressive ratio schedule were conducted to examine this possibility. These findings suggest the treatments employed could serve as an effect component in the treatment of cocaine addiction. Financial Support: Research was supported by NIH grants P50 DA033942-02 (MEC) and T32-DA007097-32. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.554 Weaving evidenced-informed, culture-based interventions into treatment in Native American and Alaska Native communities Anne Helene Skinstad 1,∗ , R. Dale Walker 2 , Jenny Gringer Richards 1 , Sean A. Bear 1 1 Community and Behavioral Health, University of Iowa, Iowa City, IA, United States 2 Psychiatry, Oregon Health and Science University and the One Sky Center, Portland, OR, United States
Aims: In the current climate of increasing mandates on the use of Evidenced Based Practices (EPB), it is becoming increasingly evident that in Indian Country, these mandates need to be tempered with a respect and appreciation for Native culture, knowledge, healing practice and a sensitivity of cultural context in order to be effective with the American Indian and Alaska Native communities. There are Native Americans (NA) holding traditional spiritual beliefs being diagnosed with psychosis and OCD while operating appropriately within the context of their traditional spiritual
beliefs. EBP were not developed nor validated within NA communities and are not necessarily a good fit for NAs given their traditional beliefs. Additionally, the concept of a mandate is in conflict with the concept of tribal sovereignty. Methods: In our project, we invited spiritual leaders and identified medicine men and women from Canada, Alaska, the Southwest, Southeast, and Upper Midwest United States to come together for a discussion on spirituality, cultural issues and treatment of behavioral disorders with non-Native behavioral health providers. This forum raised awareness by providing education and a dialogue between NA spiritual leaders and providers. This approach leads to dissemination of knowledge within the behavioral health workforce. Results: Through the education of providers, we can help them provide more culturally informed care to their NA clients and, subsequently help NA achieve better health. Conclusions: Appropriate diagnosis and treatment must occur with respect and as much understanding of the cultural context (and the clients’ level of assimilation) as is possible in order to be effective. Financial Support: This project is funded by SAMHSA. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.555 The effects of strength training on heroin self-administration Mark A. Smith ∗ , Gaylen Fronk, Sarah Bills, Ryan Lacy Davidson College, Davidson, NC, United States Aims: Previous studies have reported that voluntary wheel running decreases drug self-administration in laboratory rats, suggesting that aerobic exercise might be an effective intervention in substance abuse treatment programs. The purpose of the present study was to examine the effects of resistance exercise (i.e., strength training) on heroin self-administration in rats responding on a fixed ratio (FR1) schedule of reinforcement. Methods: Female, Long-Evans rats were obtained as young adults and assigned to exercising or sedentary conditions. Exercising rats climbed a vertical ladder wearing a weighted vest and were trained 6 days/week for the duration of the study. Training in this group used a three-set “pyramid” in which the number of repetitions and amount of resistance varied across three sets: 8 climbs carrying 70% body weight (BW), 6 climbs carrying 85% BW, and 4 climbs carrying 100% BW. Sedentary control rats were placed repeatedly on the ladder turned horizontally on its side to equate handling and exposure to the apparatus. After 3 weeks, rats were implanted with intravenous catheters and heroin selfadministration was examined on an FR1 schedule of reinforcement. Results: Heroin self-administration was significantly lower in exercising rats than sedentary rats when responding was maintained by low and moderate doses of heroin. These effects were not due to nonspecific differences in operant responding because no differences were observed in responding during a saline substitution test. Conclusions: These data indicate that resistance exercise decreases the positive reinforcing effects of heroin and suggest that strength training may be an effective intervention for opioid use disorders. Financial Support: NIDA grants R01DA031725 (MAS) and R01DA0274855 (MAS). http://dx.doi.org/10.1016/j.drugalcdep.2015.07.556
Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
Treating impulsivity for cocaine and food in female and male rats by repurposing therapeutics John R. Smethells ∗ , Marilyn E. Carroll University of Minnesota, St. Paul, MN, United States Aims: The ability to engage in recreation drug use requires one to forgo drug use until an appropriate time and place. For instance, many problem users are prone to consume drugs throughout the day, including at work. Treating such compulsions is an important component in treating individuals with drug abuse problems. Methods: The present research modeled impulsive choice for cocaine and food in rats. Specifically female and male rats were given a choice between a larger-later and smaller-sooner alternative. In some conditions, choices were between amounts of food (1 or 3 food pellets) and in others, doses of cocaine (.3 mg/kg or .9 mg/kg infusions of cocaine). In both conditions, once preference for the large alternative was established, delays to the large alternative were introduced and increased each session in ascending order (7.5, 15, 30, 60 sec). Following establishment of a delay gradient (large preference decreased across delay), rats were treated with Progesterone (.05 mg/kg), Atomoxetine (1.5 mg/kg) or together as a combination treatment to determine how they altered impulsivity for food and cocaine. Results: Rats’ preference for the large alternative decreased with increases in large-alternative delay to form a delay gradient. When choosing between doses of cocaine, treatment with Atomoxetine and Progesterone decreased impulsivity (increased large alternative preference relative to baseline) compared to vehicle control in female rats. However, when choosing between amounts of food, neither treatment altered impulsive choice compared to baseline. Conclusions: The initial findings suggest that both Progesterone and Atomoxetine reduce impulsivity for cocaine, but not impulsivity for food. A mechanism thought to the effect is that these treatments reduce the reinforcing efficacy of cocaine; follow-up studies employing a progressive ratio schedule were conducted to examine this possibility. These findings suggest the treatments employed could serve as an effect component in the treatment of cocaine addiction. Financial Support: Research was supported by NIH grants P50 DA033942-02 (MEC) and T32-DA007097-32. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.554 Weaving evidenced-informed, culture-based interventions into treatment in Native American and Alaska Native communities Anne Helene Skinstad 1,∗ , R. Dale Walker 2 , Jenny Gringer Richards 1 , Sean A. Bear 1 1 Community and Behavioral Health, University of Iowa, Iowa City, IA, United States 2 Psychiatry, Oregon Health and Science University and the One Sky Center, Portland, OR, United States
Aims: In the current climate of increasing mandates on the use of Evidenced Based Practices (EPB), it is becoming increasingly evident that in Indian Country, these mandates need to be tempered with a respect and appreciation for Native culture, knowledge, healing practice and a sensitivity of cultural context in order to be effective with the American Indian and Alaska Native communities. There are Native Americans (NA) holding traditional spiritual beliefs being diagnosed with psychosis and OCD while operating appropriately within the context of their traditional spiritual
beliefs. EBP were not developed nor validated within NA communities and are not necessarily a good fit for NAs given their traditional beliefs. Additionally, the concept of a mandate is in conflict with the concept of tribal sovereignty. Methods: In our project, we invited spiritual leaders and identified medicine men and women from Canada, Alaska, the Southwest, Southeast, and Upper Midwest United States to come together for a discussion on spirituality, cultural issues and treatment of behavioral disorders with non-Native behavioral health providers. This forum raised awareness by providing education and a dialogue between NA spiritual leaders and providers. This approach leads to dissemination of knowledge within the behavioral health workforce. Results: Through the education of providers, we can help them provide more culturally informed care to their NA clients and, subsequently help NA achieve better health. Conclusions: Appropriate diagnosis and treatment must occur with respect and as much understanding of the cultural context (and the clients’ level of assimilation) as is possible in order to be effective. Financial Support: This project is funded by SAMHSA. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.555 The effects of strength training on heroin self-administration Mark A. Smith ∗ , Gaylen Fronk, Sarah Bills, Ryan Lacy Davidson College, Davidson, NC, United States Aims: Previous studies have reported that voluntary wheel running decreases drug self-administration in laboratory rats, suggesting that aerobic exercise might be an effective intervention in substance abuse treatment programs. The purpose of the present study was to examine the effects of resistance exercise (i.e., strength training) on heroin self-administration in rats responding on a fixed ratio (FR1) schedule of reinforcement. Methods: Female, Long-Evans rats were obtained as young adults and assigned to exercising or sedentary conditions. Exercising rats climbed a vertical ladder wearing a weighted vest and were trained 6 days/week for the duration of the study. Training in this group used a three-set “pyramid” in which the number of repetitions and amount of resistance varied across three sets: 8 climbs carrying 70% body weight (BW), 6 climbs carrying 85% BW, and 4 climbs carrying 100% BW. Sedentary control rats were placed repeatedly on the ladder turned horizontally on its side to equate handling and exposure to the apparatus. After 3 weeks, rats were implanted with intravenous catheters and heroin selfadministration was examined on an FR1 schedule of reinforcement. Results: Heroin self-administration was significantly lower in exercising rats than sedentary rats when responding was maintained by low and moderate doses of heroin. These effects were not due to nonspecific differences in operant responding because no differences were observed in responding during a saline substitution test. Conclusions: These data indicate that resistance exercise decreases the positive reinforcing effects of heroin and suggest that strength training may be an effective intervention for opioid use disorders. Financial Support: NIDA grants R01DA031725 (MAS) and R01DA0274855 (MAS). http://dx.doi.org/10.1016/j.drugalcdep.2015.07.556