Modulation of reinstated polydrug (cocaine/heroin) seeking by noradrenergic α2 agonists

Abstract

Drug and Alcohol Dependence 156 (2015) e183–e245 e209 the amount spent on cocaine as a predictor of smoking (p=0.01). Specifically, patients receiving MAS-XR spent $43 more on cocaine to increase their smoking by 1 cigarette, while patients receiving placebo spent $56 more on cocaine for the same result. Conclusions: Cocaine use correlates with smoking habits in bothMAS-XR and placebo treated patients. For thosewho continue to use cocaine, MAS-XR with concurrent cocaine use may trigger greater smoking among ADHD/cocaine dependent smokers when compared to the placebo group. Financial Support: NIDA:1R25DA03516101 RFMH:1RO1DA23652/RO1DA23651. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.562 Modulation of reinstated polydrug (cocaine/heroin) seeking by noradrenergic 2 agonists Roger D. Spealman1,∗, Jack Bergman2 1 New England Primate Research Center, Harvard Medical School, Southborough, MA, United States 2 McLean Hospital, Harvard Medical School, Belmont, MA, United States Aims: Noradrenergic 2 agonists can alleviate opioid withdrawal and have been proposed for prevention of relapse to stimulant abuse. We investigated the potential of these drugs for attenuating relapse to polydrug (cocaine/heroin) abuse using a nonhuman primate model of reinstated drug seeking. Methods: Squirrelmonkeyswere trained to respondunder concurrent second-order FR10 (FR5:S) schedules of i.v. cocaine/heroin (10:1) self-administration and milk delivery. Responding on the drug-associated lever subsequently was reduced to <10% of baseline by discontinuing drug injections and presentations of the drug-paired stimulus, while keeping the concurrent schedule of milk delivery intact.We next determined the degree to which drug seeking could be reinstated by: (1) restoring the drug-paired stimulus, (2) primingwith a 10:1 cocaine/heroinmixture, or (3) priming + restoration of the drug-paired stimulus. Each conditionwas studied after pretreatmentwith vehicle or doses of 2 agonists that had no significant effects on an inventory of unconditioned behaviors: 0.1mg/kg clonidine, 0.1mg/kg lofexidine, 1.0mg/kg guanfacine, and 0.03mg/kg brimonidine. Results: Pretreatment with each 2 agonist attenuated reinstatement of drug-seeking induced by cocaine/heroin priming and had less effect on reinstatement induced by the drug-paired stimulus. Clonidine, lofexidine, and guanfacine also attenuated the more pronounced reinstatement induced by priming + restoration of the drug-paired stimulus. Additionally, clonidine and lofexidine reduced% responding on the drug-associated leverwhen reinstatement was induced by priming alone and/or priming + restoration of the drug-paired stimulus. Conclusions: The profile of effects seen with clonidine and lofexidine (attenuation of reinstated responding with a reduction in% responding ondrug lever) suggests a selective effect of these 2 agonists on reinstated drug seeking and encourages further evaluation of their potential for polydrug relapse prevention. Financial Support: NIH grants DA031299, RR00168 and OD011103. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.563 Applying SBIRT to new settings: Preliminary findings of substance use disorder risk in community mental health settings Suzanne E. Spear2,∗, Mitch Karno3, Suzette Glasner-Edwards3, R. Rawson3, Richard Saitz1, Blanca Dominguez3 1 Community Health Sciences, Boston University and Boston Medical Center, Boston, MA, United States 2 Health Sciences, California State University, Northridge, Northridge, CA, United States 3 Psychiatry, UCLA Integrated Substance Abuse Programs, Los Angeles, CA, United States Aims: Screening, Brief Intervention, and Referral to Treatment (SBIRT) has not yet been tested in community mental health treatment settings despite the elevated risk of substance use disorders (SUD) among individuals with mental health disorders. This presentation reports on preliminary findings of SUD risk among 334 adult participants treated in community mental health clinics in Southern California. SUD risk was calculated from the AUDIT and DAST-10 screening tools. Methods: All participants are currently enrolled in a randomized controlled trial of SBIRT. Participants were recruited from four outpatient clinics and one inpatient clinic. High risk for SUDs was defined by scores on the AUDIT (≥13 for women and ≥15 for men) and the DAST-10 (≥3 for women and men). Associations between SUD risk and presence of mood disorders, anxiety disorders, and psychotic disorders were examined using chi-square tests. Results: Results showed that 37% of participants were at high risk for alcohol disorders and 66% of participants were at high risk for illicit drug use disorders. Alcohol disorder risk was significantly associated with mood disorders ( 2 =13.25, p< .01) and anxiety disorders ( 2 =8.6, p< .05). Illicit drug use disorder risk was significantly associated with anxiety disorders ( 2 =25.96, p< .001). Presence of psychotic disorders was not associated with SUD risk. Conclusions: High rates of SUD risk in this community mental health sample were found. Participants with mood and/or anxiety disorders were found to be at high risk of SUDs. Subsequent research will test the efficacy of SBIRT for reducing SUD risk and linking participants with possible SUDs to treatment. Financial Support: Supported by NIDA grant R01DA032733. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.564 Prescription monitoring programs: Best practice and Canadian program review