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Heroin) Mixtures By Alpha-2 Agonists
Abstracts / Drug and Alcohol Dependence 146 (2015) e34–e117
Risky behaviors on the road: Do women and men act differently after drinking? Tanara R. Sousa 1 , Graciela Pasa 1 , Jeffrey Lunnen 2 , Flavio P. Pechansky 1 1 Center for Drug and Alcohol Research, Federal University of Rio Grande do Sul, Porto Alegre, Brazil 2 Johns Hopkins International Injury Research Unit, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
Aims: To compare differences between female and male drivers regarding select risk factors in two Brazilian cities receiving intervention as part of the Global Road Safety Project. Methods: A knowledge, attitude and perception (KAP) survey was conducted among drivers in Palmas and Teresina. In October and November 2013, 1556 face to face interviews were conducted; sampling was done by quotas, according to driver’s sex (70.9% male) and age. Results: The results show that females and males behave differently on the road. Females reported drinking and driving less (41.1% vs. 64.9% – p < 0.001), and reported being a passenger to someone who had been drinking more (51.9% vs. 40.2% – p < 0.001). Females who reported binge drinking drove under the influence more than females who had not (55.2% vs. 29.1% – p < 0.001). Regarding involvement in a road traffic crash while under the influence of alcohol, 11.8% of males reported having this experience in their life as compared to 1.1% of females (p < 0.001). Conclusions: Males represent the most vulnerable road user group due to their being more prone to road traffic crashes and engaging in risky behaviors such as drinking and driving. Similar to global patterns, we found a greater proportion of males engaging in drinking and driving, and experiencing a road traffic crash while under the influence than their female counterparts. However, females self-reported more drink driving associated with binge drinking, and being a passenger of a drunk driver after drinking themselves. These results indicate intervention activities may be tailored to address risky behavior among males, but should also discourage other risk behaviors related to drinking among the general population. Financial support: This study is supported by Bloomberg Philanthropies. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.652 Modulation Of Behavioral Effects Of Polydrug (Cocaine/Heroin) Mixtures By Alpha-2 Agonists Roger D. Spealman 1,∗ , Jack Bergman 2 1 Behavioral Biology-NERPRC, Harvard Medical School, Southborough, MA 2 Preclinical Pharmacology, McLean Hospital-Harvard Medical School, Belmont, MA
Aims: Noradrenergic alpha-2 agonists have been reported to attenuate opioid withdrawal and proposed as possible anti-relapse medications for cocaine and heroin addiction. We investigated the ability of selected alpha-2 agonists to attenuate behavioral effects of cocaine/heroin mixtures that are associated with addiction liability. Methods: First, dose-response curves were determined for i.m. clonidine, lofexidine, guanfacine, and brimonidine (UK 14304) in squirrel monkeys using quantitative observational procedures. Next, the modulation of discriminative-stimulus and reinforcing effects of cocaine/heroin mixtures by selected doses of alpha-2 agonists was examined in separate groups of subjects
e105
Results: All drugs produced dose-related sedative-like effects characterized by an increase in species-typical sleep/rest posture and decreases in locomotor activity and environmentally directed behaviors. Impaired balance and muscle relaxation were noted occasionally at the highest doses. Based on their ED min values, the order of potency was: brimonidine (0.1 mg/kg) > lofexidine (0.3 mg/kg) = clonidine (0.3 mg/kg) > guanfacine (1.8 mg/kg). In drug discrimination studies, the discriminative stimulus effects of a cocaine-heroin mixture were not significantly altered by doses of brimonidine, guanfacine or clonidine below those that produced sedative effects and decreased operant responding to < 50% of control values. Ongoing self-administration ‘choice’ studies suggest that daily treatment with clonidine (0.1 or 0.18 mg/kg) leads to a diminution of its sedating effects but continues to produce a > 50% decrease in the intake of cocaine/heroin mixtures without consistent modulation of their reinforcing strength. Conclusions: These data indicate that doses of alpha-2 agonists with behavioral side-effects that diminish over repeated treatment may be useful for in the management of polydrug (cocaine/heroin) addiction. Financial Support: (supported by DA 031299) http://dx.doi.org/10.1016/j.drugalcdep.2014.09.653 Differential effects of the benzodiazepines alprazolam and oxazepam on methamphetamine-related behaviors in rats Allyson Spence, Glenn F. Guerin, Nicholas E. Goeders Pharmacology, Toxicology, & Neuroscience, LSU Health Sciences Center, Shreveport, LA, United States Aims: Drug users often combine benzodiazepines with psychostimulants, such as methamphetamine (METH). Previous research has shown that not all benzo-diazepines have the same potential for abuse. While alprazolam (ALP) is highly preferred by drug users, oxazepam (OX) has a far lower abuse potential. We hypothesized that METH would induce conditioned place preference (CPP), while OX and ALP would block the METH-induced CPP. We hypothesized that OX and ALP would attenuate METH discrimination. Methods: CPP was conducted to study the reward potential of the benzodiaz-epines OX and ALP when combined with METH to simulate polydrug abuse in rats (n = 8/group). To determine if ALP and/or OX would alter the subjective effects of METH, we also investigated the effects of these drugs on the discriminative stimulus effects of METH in rats (n = 7/group). Rats were trained to discriminate METH (1.0 mg/kg, ip) from saline using a two-lever operant, food-reinforced, drug discrimination design. The effects of ALP (2 and 4 mg/kg, ip) and OX (5, 10, and 20 mg/kg, ip) on METH discrimination were determined by administering these drugs prior to various doses of METH (0, 0.125, 0.25, 0.5, 1, or 2 mg/kg, ip) and then measuring whether the rat pressed the METH- or saline-associated lever. Data were analyzed using one-way ANOVA. Results: METH produced a CPP, and OX blocked this METHinduced CPP. However, ALP did not block the METH-induced CPP. OX significantly attenuated METH discrimination in rats. However, we found that the high dose of ALP augmented the subjective effects of lower doses of METH. Conclusions: The results of these experiments suggest that OX and ALP can differentially affect meth-related behaviors. OX attenuates the rewarding properties as well as the subjective effects of METH, while ALP may actually increase the rewarding properties of lower doses of METH. Future research will aim to identify the
Risky behaviors on the road: Do women and men act differently after drinking? Tanara R. Sousa 1 , Graciela Pasa 1 , Jeffrey Lunnen 2 , Flavio P. Pechansky 1 1 Center for Drug and Alcohol Research, Federal University of Rio Grande do Sul, Porto Alegre, Brazil 2 Johns Hopkins International Injury Research Unit, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
Aims: To compare differences between female and male drivers regarding select risk factors in two Brazilian cities receiving intervention as part of the Global Road Safety Project. Methods: A knowledge, attitude and perception (KAP) survey was conducted among drivers in Palmas and Teresina. In October and November 2013, 1556 face to face interviews were conducted; sampling was done by quotas, according to driver’s sex (70.9% male) and age. Results: The results show that females and males behave differently on the road. Females reported drinking and driving less (41.1% vs. 64.9% – p < 0.001), and reported being a passenger to someone who had been drinking more (51.9% vs. 40.2% – p < 0.001). Females who reported binge drinking drove under the influence more than females who had not (55.2% vs. 29.1% – p < 0.001). Regarding involvement in a road traffic crash while under the influence of alcohol, 11.8% of males reported having this experience in their life as compared to 1.1% of females (p < 0.001). Conclusions: Males represent the most vulnerable road user group due to their being more prone to road traffic crashes and engaging in risky behaviors such as drinking and driving. Similar to global patterns, we found a greater proportion of males engaging in drinking and driving, and experiencing a road traffic crash while under the influence than their female counterparts. However, females self-reported more drink driving associated with binge drinking, and being a passenger of a drunk driver after drinking themselves. These results indicate intervention activities may be tailored to address risky behavior among males, but should also discourage other risk behaviors related to drinking among the general population. Financial support: This study is supported by Bloomberg Philanthropies. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.652 Modulation Of Behavioral Effects Of Polydrug (Cocaine/Heroin) Mixtures By Alpha-2 Agonists Roger D. Spealman 1,∗ , Jack Bergman 2 1 Behavioral Biology-NERPRC, Harvard Medical School, Southborough, MA 2 Preclinical Pharmacology, McLean Hospital-Harvard Medical School, Belmont, MA
Aims: Noradrenergic alpha-2 agonists have been reported to attenuate opioid withdrawal and proposed as possible anti-relapse medications for cocaine and heroin addiction. We investigated the ability of selected alpha-2 agonists to attenuate behavioral effects of cocaine/heroin mixtures that are associated with addiction liability. Methods: First, dose-response curves were determined for i.m. clonidine, lofexidine, guanfacine, and brimonidine (UK 14304) in squirrel monkeys using quantitative observational procedures. Next, the modulation of discriminative-stimulus and reinforcing effects of cocaine/heroin mixtures by selected doses of alpha-2 agonists was examined in separate groups of subjects
e105
Results: All drugs produced dose-related sedative-like effects characterized by an increase in species-typical sleep/rest posture and decreases in locomotor activity and environmentally directed behaviors. Impaired balance and muscle relaxation were noted occasionally at the highest doses. Based on their ED min values, the order of potency was: brimonidine (0.1 mg/kg) > lofexidine (0.3 mg/kg) = clonidine (0.3 mg/kg) > guanfacine (1.8 mg/kg). In drug discrimination studies, the discriminative stimulus effects of a cocaine-heroin mixture were not significantly altered by doses of brimonidine, guanfacine or clonidine below those that produced sedative effects and decreased operant responding to < 50% of control values. Ongoing self-administration ‘choice’ studies suggest that daily treatment with clonidine (0.1 or 0.18 mg/kg) leads to a diminution of its sedating effects but continues to produce a > 50% decrease in the intake of cocaine/heroin mixtures without consistent modulation of their reinforcing strength. Conclusions: These data indicate that doses of alpha-2 agonists with behavioral side-effects that diminish over repeated treatment may be useful for in the management of polydrug (cocaine/heroin) addiction. Financial Support: (supported by DA 031299) http://dx.doi.org/10.1016/j.drugalcdep.2014.09.653 Differential effects of the benzodiazepines alprazolam and oxazepam on methamphetamine-related behaviors in rats Allyson Spence, Glenn F. Guerin, Nicholas E. Goeders Pharmacology, Toxicology, & Neuroscience, LSU Health Sciences Center, Shreveport, LA, United States Aims: Drug users often combine benzodiazepines with psychostimulants, such as methamphetamine (METH). Previous research has shown that not all benzo-diazepines have the same potential for abuse. While alprazolam (ALP) is highly preferred by drug users, oxazepam (OX) has a far lower abuse potential. We hypothesized that METH would induce conditioned place preference (CPP), while OX and ALP would block the METH-induced CPP. We hypothesized that OX and ALP would attenuate METH discrimination. Methods: CPP was conducted to study the reward potential of the benzodiaz-epines OX and ALP when combined with METH to simulate polydrug abuse in rats (n = 8/group). To determine if ALP and/or OX would alter the subjective effects of METH, we also investigated the effects of these drugs on the discriminative stimulus effects of METH in rats (n = 7/group). Rats were trained to discriminate METH (1.0 mg/kg, ip) from saline using a two-lever operant, food-reinforced, drug discrimination design. The effects of ALP (2 and 4 mg/kg, ip) and OX (5, 10, and 20 mg/kg, ip) on METH discrimination were determined by administering these drugs prior to various doses of METH (0, 0.125, 0.25, 0.5, 1, or 2 mg/kg, ip) and then measuring whether the rat pressed the METH- or saline-associated lever. Data were analyzed using one-way ANOVA. Results: METH produced a CPP, and OX blocked this METHinduced CPP. However, ALP did not block the METH-induced CPP. OX significantly attenuated METH discrimination in rats. However, we found that the high dose of ALP augmented the subjective effects of lower doses of METH. Conclusions: The results of these experiments suggest that OX and ALP can differentially affect meth-related behaviors. OX attenuates the rewarding properties as well as the subjective effects of METH, while ALP may actually increase the rewarding properties of lower doses of METH. Future research will aim to identify the