- Email: [email protected]
3 agonism attenuate ethanol-reinforced appetitive responding
Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
Stable housing, stable substance use? Evaluation of two ‘Housing First’ programs for homeless individuals Elizabeth Whittaker ∗ , Lucy Burns National Drug and Alcohol Research Centre, UNSW, Sydney, NSW, Australia Aims: Australian and international evidence highlights the heightened prevalence of substance use disorders in homeless populations. In recent years, adaptions of the Housing First initiative, whereby chronically homeless individuals are provided long-term housing with support, have been implemented across Australia. Two such adaptions include scatter-site (private rental apartments; SS) and congregate site (apartments in the one building; CS) models. There is currently limited Australian evidence on the effect that these variations of Housing First programs have on client outcomes. The primary aim of this study was to undertake a longitudinal evaluation of two adaptations of the Housing First model (one SS and one CS) in relation to clients’ housing and health outcomes, specifically substance use patterns and service utilisation. Methods: Longitudinal mixed-methods design comparing process and outcome measures at baseline and 12 months postbaseline. Results: A recruitment rate of 67% was achieved at baseline for both programs, of which 78% were successfully followed-up at 12 months post-baseline. Clients in both models did not differ significantly on demographics, homelessness history or proportion with a substance use disorder. However, at baseline a significantly higher proportion of clients in the CS model had an anxiety disorder (67% vs. 34%) and had recently injected (42% vs. 19%). Findings over time showed that whilst injecting behaviour reduced in the SS model (19–11%), it remained unchanged in the CS model. Whereas deceasing trends were observed for all justice system outcomes in the SS model, overall increases were found for the CS model. Conclusions: A number of factors distinguished outcomes in the two Housing First models. Clients entering the CS model appeared to be less well and were injecting drugs more often, suggesting high rates of illicit drug dependence. Financial support: New South Wales Department of Housing. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.643 Oral JPC-077 and JPC-141, vesicular monoamine transporter-2 inhibitors, reduce methamphetamine self-administration and methamphetamine-induced reinstatement in rats A. George Wilson 1,∗ , Justin Nickell 1 , John P. Culver 1 , Venumadhav Janganati 2 , Guangrong Zheng 2 , Peter A. Crooks 2 , Linda P. Dwoskin 1 , Michael T. Bardo 1 1
University of Kentucky, Lexington, KY, United States University of Arkansas for Medical Science, Little Rock, AR, United States 2
Aims: Recently, we synthesized a series of compounds that may aid in reducing methamphetamine (METH) abuse and relapse. These compounds, 1,4-diphenethyl analogs of lobelane (a defunctionalized derivative of lobeline), are potent and selective vesicular monoamine transporter-2 (VMAT-2) inhibitors. Here, we report the effects of oral administration of two analogs from this series (JPC077 and JPC-141) on METH self-administration and reinstatement in rats.
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Methods: After surgical implantation of a jugular catheter, rats learned that METH infusions (0.05 mg/kg) could be earned via responding. To assess the effect of JPC-077 and JPC-141 on METH self-administration, rats (n = 6/compound) earned infusions 15 min after gavage with compound. To assess METH-induced reinstatement, a separate group of rats (n = 5/compound) experienced similar training then underwent 10 extinction sessions. During three test sessions, subjects were gavaged with two doses of compound or vehicle alone while receiving a METH (0.5 mg/kg) i.p. injection to induce METH-seeking. Results: JPC-077 (100,170 and 300 mg/kg) reduced METH self-administration. Further, JPC-077 at 100 and 300 mg/kg blocked METH-induced reinstatement. JPC-141 (130 and 170 mg/kg) reduced METH self-administration. Likewise, JPC-141 (130 and 170 mg/kg) blocked METH-induced reinstatement. Conclusions: JPC-077 and JPC-141 reduced both METH selfadministration and reinstatement. Importantly, doses of JPC-077 that blocked METH self-administration and reinstatement were approximately three-times lower than those required to significantly reduce locomotor activity (previous work from our laboratory), indicating that current results were not due to nonspecific suppressant effects. Thus, JPC-077 and JPC-141 represent novel orally bioavailable leads for treating METH abuse. Financial support: NIDA grant U01DA013519. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.644 Systemic and intraaccumbens mGluR2/3 agonism attenuate ethanol-reinforced appetitive responding Kyle A. Windisch 2,1,∗ , Cristine L. Czachowski 2 1
Rockefeller University, Indianapolis, IN, United States 2 Psychology, IUPUI, Indianapolis, IN, United States Aims: Previous studies suggest that group II metabotropic glutamate receptors (mGluR2/3) are involved in regulating ethanol (EtOH) drinking and seeking following extinction. The sipper tube model, which allows for procedural separation of seeking and intake, was used to further clarify the role of mGluR2/3 in EtOH-seeking and consumption. A microinjection study was also performed to examine the role of nucleus accumbens (NAc) core mGluR2/3 in EtOH-seeking using the mGluR2/3 antagonist LY341495 (LY34). Methods: For the systemic agonist experiments, male Wistar rats [n = 8–9 group; LY379268 (LY37) (0–2.0 mg/kg)] were trained to complete a response requirement (RR) of 10 lever presses that resulted in access to 10% EtOH or 2% sucrose (in separate groups) for a 20-min drinking period. For drinking testing, weekly drug injections preceded a RR1. The RR was then increased over sessions to a RR20. For seeking testing, weekly drug injections preceded a non-reinforced extinction session. To determine effects of blockade of NAc core mGluR2/3 on agonist-induced suppression of EtOHseeking, a separate group of rats (n = 15) was trained to complete a RR10 for access to 10% EtOH. Animals were implanted with bilateral NAc core cannulae and then received four sets of injections in a balanced design (Systemic + core: vehicle + vehicle, LY37 + vehicle, LY37 + LY34, and vehicle + LY34) and a final non-balanced LY37 microinjection. Results: Systemic administration of the mGluR2/3 agonist LY37 significantly reduced EtOH- and sucrose-seeking with no systematic effect on locomotion. Systemic LY37 also significantly reduced sucrose consumption. NAc core LY34 did not block the effects of LY37, but LY37 in the core also significantly reduced EtOH-seeking.
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Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
Conclusions: These findings suggest that modulation of glutamatergic neurotransmission by systemic LY37 significantly reduces general reinforcer seeking. Suppression of EtOH-seeking following NAc core LY37 suggests that NAc core mGluR2/3 are involved in modulating EtOH-seeking during maintenance drinking. Financial support: NIAAA T32AA07462. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.645 Pilot evaluation of the “tailored telephone intervention delivered by peers to prevent recurring opioid-overdoses” Theresa Winhusen ∗ , Jeff Theobald, Daniel Lewis, Christine M. Wilder, Michael Lyons University of Cincinnati, Cincinnati, OH, United States Aims: Individuals experiencing non-fatal opioid-overdose (OOD) are at heightened risk for future OODs. To date, there are no validated interventions targeting these patients. We created and piloted TTIP-PRO, a computer-facilitated, peer-delivered, individually-tailored intervention designed to (1) increase patient knowledge about OOD, and (2) encourage patients to initiate medication assisted treatment (MAT). Methods: Two peer interventionists, individuals who have been abstinent from illicit opioids for at least a year, enrolled in MAT, and have personal experience with OOD, were recruited from the institution’s MAT clinic by word of mouth; the outcomes of interest were their ability to complete training and certification and their feedback on implementing TTIP-PRO. Recruitment letters were sent to patients treated for OOD in the UC emergency department within the prior 8 months. Eight patients received the TTIP-PRO intervention combined with assessment before and after. Outcomes of interest were participant satisfaction with TTIP-PRO and pre-post change in (1) knowledge about OOD (risk factors for OOD, signs of OOD, appropriate response to OOD, and MAT), and (2) interest in initiating MAT. Results: Both peer interventionists completed training and certification within the designated 4 h time-frame and rated their satisfaction with providing TTIP-PRO as 4 on a 4-point scale (4.0, SD = 0.0). Participants’ OOD knowledge increased significantly, with 69.9% (SD = 12.5%) correct responses pre-TTIP-PRO and 93.6% (SD = 2.5%) correct responses post-TTIP-PRO (W = 8, p = .0078). Participant interest in receiving MAT, measured on a 10-point scale, increased from 8.1 (SD = 3.2) pre-TTIP-PRO to 9.5 (SD = 1.1) postTTIP-PRO, but this was not statistically significant (W = 3, p = .25), likely reflecting a ceiling effect (5 of the 8 participants had a prerating of 10). All participants rated the helpfulness of TTIP-PRO at the maximum on a 4-point scale (4.0, SD = 0.0). Conclusions: A larger study of TTIP-PRO may be warranted. Financial support: University of Cincinnati. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.646
Parents as interventionists to address adolescent drug abuse Ken Winters 1,2 1
University of Minnesota Medical School, Minneapolis, MN, United States 2 Treatment Research Institute, Philadelphia, PA, United States Aims: The importance of parents as “interventionists” is supported by reviews of the treatment literature as well as the emerging science that home-based initiatives by parents can contribute to desired health changes in adolescents. The aim of this study is to investigate the efficacy of an indicated preventive intervention in which parents were taught skills in motivational interviewing and psycho-educational counseling, and with assistance from a coach, they delivered the program in the home to their drug abusing teenager. This paper will report the 6-month outcome data. Methods: A detailed manual for parents was developed. Consisting of four sessions, the program’s content stressed strengthening parental communication skills; improving parental monitoring of the adolescent’s compliance with family drug-free expectations; and strengthening commitment to assist the child to cope with drug triggers. Delivery of the program in the home was to occur across 4 weeks. Families were randomly assigned to this target condition (n = 82) or to a control group (n = 68) (manual adjusted to be education-based and no coaching was included). Assessments occurred at baseline, and 6- and 12-months post intervention. Results: Based on 6-month outcome data, adolescents in the target condition showed significant improvement on all drug involvement variables (marijuana and alcohol use frequency; rates of marijuana and alcohol abstinence; count of drug problems and SUD symptoms) compared to adolescents in the control condition. The exception was that the groups did not differ in terms of changes in psychological distress variables (equal reduction in both groups). A significant mediator of intervention effects was parent-child relations; improvement in family solidary was associated with reduced drug use involvement. Conclusions: These findings offer provisional support for the view that parents can engage their drug-using teenager in an interventionist role, and this engagement may contribute to reduced drug involvement by their teenage son or daughter. Financial support: NIDA grants P50-DA027841 and K24DA035882. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.647 Using behavioral economics to predict opioid use during prescription opioid dependence treatment
Matthew Worley 1,∗ , Steven Shoptaw 1 , Warren K. Bickel 2 , Walter Ling 3 1 University of California, Los Angeles, Los Angeles, CA, United States 2 Addiction Recovery and Research Center, Virginia Tech Carilion Research Institute, Roanoke, VA, United States 3 UCLA, Integrated Substance Abuse, Los Angeles, CA, United States
Aims: Research using behavioral economics has previously linked addictive behavior to disrupted decision-making, rewardprocessing, and drug reinforcement value. These principles have not been examined in prescription opioid addiction, which is
Stable housing, stable substance use? Evaluation of two ‘Housing First’ programs for homeless individuals Elizabeth Whittaker ∗ , Lucy Burns National Drug and Alcohol Research Centre, UNSW, Sydney, NSW, Australia Aims: Australian and international evidence highlights the heightened prevalence of substance use disorders in homeless populations. In recent years, adaptions of the Housing First initiative, whereby chronically homeless individuals are provided long-term housing with support, have been implemented across Australia. Two such adaptions include scatter-site (private rental apartments; SS) and congregate site (apartments in the one building; CS) models. There is currently limited Australian evidence on the effect that these variations of Housing First programs have on client outcomes. The primary aim of this study was to undertake a longitudinal evaluation of two adaptations of the Housing First model (one SS and one CS) in relation to clients’ housing and health outcomes, specifically substance use patterns and service utilisation. Methods: Longitudinal mixed-methods design comparing process and outcome measures at baseline and 12 months postbaseline. Results: A recruitment rate of 67% was achieved at baseline for both programs, of which 78% were successfully followed-up at 12 months post-baseline. Clients in both models did not differ significantly on demographics, homelessness history or proportion with a substance use disorder. However, at baseline a significantly higher proportion of clients in the CS model had an anxiety disorder (67% vs. 34%) and had recently injected (42% vs. 19%). Findings over time showed that whilst injecting behaviour reduced in the SS model (19–11%), it remained unchanged in the CS model. Whereas deceasing trends were observed for all justice system outcomes in the SS model, overall increases were found for the CS model. Conclusions: A number of factors distinguished outcomes in the two Housing First models. Clients entering the CS model appeared to be less well and were injecting drugs more often, suggesting high rates of illicit drug dependence. Financial support: New South Wales Department of Housing. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.643 Oral JPC-077 and JPC-141, vesicular monoamine transporter-2 inhibitors, reduce methamphetamine self-administration and methamphetamine-induced reinstatement in rats A. George Wilson 1,∗ , Justin Nickell 1 , John P. Culver 1 , Venumadhav Janganati 2 , Guangrong Zheng 2 , Peter A. Crooks 2 , Linda P. Dwoskin 1 , Michael T. Bardo 1 1
University of Kentucky, Lexington, KY, United States University of Arkansas for Medical Science, Little Rock, AR, United States 2
Aims: Recently, we synthesized a series of compounds that may aid in reducing methamphetamine (METH) abuse and relapse. These compounds, 1,4-diphenethyl analogs of lobelane (a defunctionalized derivative of lobeline), are potent and selective vesicular monoamine transporter-2 (VMAT-2) inhibitors. Here, we report the effects of oral administration of two analogs from this series (JPC077 and JPC-141) on METH self-administration and reinstatement in rats.
e239
Methods: After surgical implantation of a jugular catheter, rats learned that METH infusions (0.05 mg/kg) could be earned via responding. To assess the effect of JPC-077 and JPC-141 on METH self-administration, rats (n = 6/compound) earned infusions 15 min after gavage with compound. To assess METH-induced reinstatement, a separate group of rats (n = 5/compound) experienced similar training then underwent 10 extinction sessions. During three test sessions, subjects were gavaged with two doses of compound or vehicle alone while receiving a METH (0.5 mg/kg) i.p. injection to induce METH-seeking. Results: JPC-077 (100,170 and 300 mg/kg) reduced METH self-administration. Further, JPC-077 at 100 and 300 mg/kg blocked METH-induced reinstatement. JPC-141 (130 and 170 mg/kg) reduced METH self-administration. Likewise, JPC-141 (130 and 170 mg/kg) blocked METH-induced reinstatement. Conclusions: JPC-077 and JPC-141 reduced both METH selfadministration and reinstatement. Importantly, doses of JPC-077 that blocked METH self-administration and reinstatement were approximately three-times lower than those required to significantly reduce locomotor activity (previous work from our laboratory), indicating that current results were not due to nonspecific suppressant effects. Thus, JPC-077 and JPC-141 represent novel orally bioavailable leads for treating METH abuse. Financial support: NIDA grant U01DA013519. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.644 Systemic and intraaccumbens mGluR2/3 agonism attenuate ethanol-reinforced appetitive responding Kyle A. Windisch 2,1,∗ , Cristine L. Czachowski 2 1
Rockefeller University, Indianapolis, IN, United States 2 Psychology, IUPUI, Indianapolis, IN, United States Aims: Previous studies suggest that group II metabotropic glutamate receptors (mGluR2/3) are involved in regulating ethanol (EtOH) drinking and seeking following extinction. The sipper tube model, which allows for procedural separation of seeking and intake, was used to further clarify the role of mGluR2/3 in EtOH-seeking and consumption. A microinjection study was also performed to examine the role of nucleus accumbens (NAc) core mGluR2/3 in EtOH-seeking using the mGluR2/3 antagonist LY341495 (LY34). Methods: For the systemic agonist experiments, male Wistar rats [n = 8–9 group; LY379268 (LY37) (0–2.0 mg/kg)] were trained to complete a response requirement (RR) of 10 lever presses that resulted in access to 10% EtOH or 2% sucrose (in separate groups) for a 20-min drinking period. For drinking testing, weekly drug injections preceded a RR1. The RR was then increased over sessions to a RR20. For seeking testing, weekly drug injections preceded a non-reinforced extinction session. To determine effects of blockade of NAc core mGluR2/3 on agonist-induced suppression of EtOHseeking, a separate group of rats (n = 15) was trained to complete a RR10 for access to 10% EtOH. Animals were implanted with bilateral NAc core cannulae and then received four sets of injections in a balanced design (Systemic + core: vehicle + vehicle, LY37 + vehicle, LY37 + LY34, and vehicle + LY34) and a final non-balanced LY37 microinjection. Results: Systemic administration of the mGluR2/3 agonist LY37 significantly reduced EtOH- and sucrose-seeking with no systematic effect on locomotion. Systemic LY37 also significantly reduced sucrose consumption. NAc core LY34 did not block the effects of LY37, but LY37 in the core also significantly reduced EtOH-seeking.
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Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
Conclusions: These findings suggest that modulation of glutamatergic neurotransmission by systemic LY37 significantly reduces general reinforcer seeking. Suppression of EtOH-seeking following NAc core LY37 suggests that NAc core mGluR2/3 are involved in modulating EtOH-seeking during maintenance drinking. Financial support: NIAAA T32AA07462. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.645 Pilot evaluation of the “tailored telephone intervention delivered by peers to prevent recurring opioid-overdoses” Theresa Winhusen ∗ , Jeff Theobald, Daniel Lewis, Christine M. Wilder, Michael Lyons University of Cincinnati, Cincinnati, OH, United States Aims: Individuals experiencing non-fatal opioid-overdose (OOD) are at heightened risk for future OODs. To date, there are no validated interventions targeting these patients. We created and piloted TTIP-PRO, a computer-facilitated, peer-delivered, individually-tailored intervention designed to (1) increase patient knowledge about OOD, and (2) encourage patients to initiate medication assisted treatment (MAT). Methods: Two peer interventionists, individuals who have been abstinent from illicit opioids for at least a year, enrolled in MAT, and have personal experience with OOD, were recruited from the institution’s MAT clinic by word of mouth; the outcomes of interest were their ability to complete training and certification and their feedback on implementing TTIP-PRO. Recruitment letters were sent to patients treated for OOD in the UC emergency department within the prior 8 months. Eight patients received the TTIP-PRO intervention combined with assessment before and after. Outcomes of interest were participant satisfaction with TTIP-PRO and pre-post change in (1) knowledge about OOD (risk factors for OOD, signs of OOD, appropriate response to OOD, and MAT), and (2) interest in initiating MAT. Results: Both peer interventionists completed training and certification within the designated 4 h time-frame and rated their satisfaction with providing TTIP-PRO as 4 on a 4-point scale (4.0, SD = 0.0). Participants’ OOD knowledge increased significantly, with 69.9% (SD = 12.5%) correct responses pre-TTIP-PRO and 93.6% (SD = 2.5%) correct responses post-TTIP-PRO (W = 8, p = .0078). Participant interest in receiving MAT, measured on a 10-point scale, increased from 8.1 (SD = 3.2) pre-TTIP-PRO to 9.5 (SD = 1.1) postTTIP-PRO, but this was not statistically significant (W = 3, p = .25), likely reflecting a ceiling effect (5 of the 8 participants had a prerating of 10). All participants rated the helpfulness of TTIP-PRO at the maximum on a 4-point scale (4.0, SD = 0.0). Conclusions: A larger study of TTIP-PRO may be warranted. Financial support: University of Cincinnati. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.646
Parents as interventionists to address adolescent drug abuse Ken Winters 1,2 1
University of Minnesota Medical School, Minneapolis, MN, United States 2 Treatment Research Institute, Philadelphia, PA, United States Aims: The importance of parents as “interventionists” is supported by reviews of the treatment literature as well as the emerging science that home-based initiatives by parents can contribute to desired health changes in adolescents. The aim of this study is to investigate the efficacy of an indicated preventive intervention in which parents were taught skills in motivational interviewing and psycho-educational counseling, and with assistance from a coach, they delivered the program in the home to their drug abusing teenager. This paper will report the 6-month outcome data. Methods: A detailed manual for parents was developed. Consisting of four sessions, the program’s content stressed strengthening parental communication skills; improving parental monitoring of the adolescent’s compliance with family drug-free expectations; and strengthening commitment to assist the child to cope with drug triggers. Delivery of the program in the home was to occur across 4 weeks. Families were randomly assigned to this target condition (n = 82) or to a control group (n = 68) (manual adjusted to be education-based and no coaching was included). Assessments occurred at baseline, and 6- and 12-months post intervention. Results: Based on 6-month outcome data, adolescents in the target condition showed significant improvement on all drug involvement variables (marijuana and alcohol use frequency; rates of marijuana and alcohol abstinence; count of drug problems and SUD symptoms) compared to adolescents in the control condition. The exception was that the groups did not differ in terms of changes in psychological distress variables (equal reduction in both groups). A significant mediator of intervention effects was parent-child relations; improvement in family solidary was associated with reduced drug use involvement. Conclusions: These findings offer provisional support for the view that parents can engage their drug-using teenager in an interventionist role, and this engagement may contribute to reduced drug involvement by their teenage son or daughter. Financial support: NIDA grants P50-DA027841 and K24DA035882. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.647 Using behavioral economics to predict opioid use during prescription opioid dependence treatment
Matthew Worley 1,∗ , Steven Shoptaw 1 , Warren K. Bickel 2 , Walter Ling 3 1 University of California, Los Angeles, Los Angeles, CA, United States 2 Addiction Recovery and Research Center, Virginia Tech Carilion Research Institute, Roanoke, VA, United States 3 UCLA, Integrated Substance Abuse, Los Angeles, CA, United States
Aims: Research using behavioral economics has previously linked addictive behavior to disrupted decision-making, rewardprocessing, and drug reinforcement value. These principles have not been examined in prescription opioid addiction, which is