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A microdialysis and behavioural investigation of modafinil in freely moving rats
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Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
their non-opioid substance use and multinomial logistic regression was used to predict these substance use groups based on type of opioid drugs used and other characteristics (demographics, pain, treatment history). Results: The most frequently used non-opioid drugs were cannabis (40%), antianxiety medications (34%) and cocaine (25%). LCA identified a 5-class (C) model. C1 (58.7%), had low risk of using non-opioid drugs. C2 (23.5%) had high risk of using anti-anxiety drugs and moderate risk of cannabis. C3 (8.8%) had high risk of using non-opioid prescription drugs (anti-anxiety, sleep, and muscle relaxant drugs) and cannabis. C4 (6.2%) had high risk of using marijuana and cocaine. C5 (2.8%) had high risk of using all nonopioid drugs. Compared to C1 (the low-using group), participants in the other classes were younger, female, tobacco users, had chronic pain, inject opioids, and used both prescription opioids and heroin. The two non-opioid prescription drug groups (C2, C3) were more likely to report chronic pain and use prescription opioids. C4 (marijuana/cocaine users) and C5 (polydrug users) were more likely to report injection. Conclusions: Aggregation of substance use may obscure important subgroup differences in patterns of illicit non-opioid drug use. The identification of two groups that primarily misuse prescription drugs and that have comparatively high rates of chronic pain suggests that self-medication may play a role among sub-groups of OTP patients. Financial support: Denver Health is part of the Researched Abuse Diversion and Addiction-Related Surveillance (RADARS® ) System. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.530 Brief HIV assessment for screening CJ offenders in addiction treatment Grace A. Rowan-Szal, G. Joe, Wayne E. Lehman, N.G. Bartholomew, K. Knight Institute of Behavioral Research, Texas Christian University, Fort Worth, TX, United States Aims: Efficient data collection in high-volume offender drugusing populations has increased demand for assessments that offer diagnostic screening of selective needs. The present study provides psychometric information on a one-page, self-report instrument of 19 items known as the TCU HVHP Form designed to provide information on HIV and hepatitis risks associated with injection drug use, sexual activities, attitudes toward condom use, and health concerns about HIV. In addition, we provide data on the predictive validity of HIV measures completed as part of a Disease Risk Reduction intervention (WaySafe). Methods: Offenders from eight prison-based treatment programs for substance abuse were assessed at intake (N = 1055). The primary instrument was the TCU HVHP along with several background assessments including motivation, psychological functioning, social functioning, and criminal thinking. The TCU WaySafe intervention assessment (administered prior to offenders exiting treatment) included five composite measures: HIV Knowledge Confidence, Avoiding Risky Sex, Avoiding Risky Drug Use, HIV Testing Awareness, and Risk Reduction Skills. Results: Principal components analysis of the HVHP form identified four scales: Injection Risk Behavior, Condom Risk, Sex Risk Behavior, and AIDS Concerns with coefficient alpha reliabilities ranging from .72 to .87. Predictive validities of the scales were demonstrated by their correlations with measures of the WaySafe intervention. The injection risk scale was significantly and negatively correlated with the avoiding risky drug use WaySafe
measure. Correspondingly, the condom risk scale was significantly correlated with the avoiding risky sex WaySafe measure. The HVHP scales had significant correlations with measures of psychological functioning including risk taking, hostility, depression, anxiety, self-esteem and decision making. Conclusions: Findings support use of this brief screening tool to help identify treatment needs in correctional settings. Financial support: Funding was provided by NIDA/NIH through a grant to TCU R01DA025885. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.531 A microdialysis and behavioural investigation of modafinil in freely moving rats H.L. Rowley 1 , R.S. Kulkarni 1 , D. Hackett 2 , David J. Heal 1 1
RenaSci Ltd, Nottingham, United Kingdom Shire Pharmacutical Development Ltd, Basingstoke, United Kingdom 2
Aims: Modafinil is a stimulant used to treat narcolepsy. Its pharmacology is enigmatic, but reports suggest modafinil is a dopamine reuptake inhibitor in human brain in vivo (Volkow et al., 2009, JAMA; 301:1148). Methods: The Culex Bambino automatically collects samples from dual micro-dialysis probes and simultaneously measures locomotor activity in freely moving rats. The effects of modafinil (100, 300 and 600 mg/kg po) on extracellular levels of noradrenaline (NA), dopamine (DA) and 5-HT in prefrontal cortex (PFC) and striatum (STR) and locomotor activity were determined ≤5 h postdosing. Results: No significant (p < 0.05) neurochemical or behavioural changes were produced by modafinil (100 mg/kg po). In PFC, modafinil (300 and 600 mg/kg) produced moderate increases in the efflux of DA (≤214%) and NA (≤263%). The onset of DA efflux was more rapid and peaked earlier (30 min) than NA (105 120 min). In STR, modafinil produced small increases of extracellular DA (≤137%) that were rapid in onset and peaked at 60 min. It had no effect on 5-HT efflux in PFC or STR. Modafinil (300 and 600 mg/kg po) dose-dependently enhanced locomotor activity. At the lower dose, rats were active for ∼2 h, whereas at the higher dose they were active throughout the 5 h experiment. No correlation existed between the increase in STR DA efflux after modafinil (600 mg/kg po) and the degree of locomotor activation (r2 = 0.002; p = 0.857). Conclusions: These data reveal that modafinil enhances neurotransmission by NA and DA in PFC and DA in STR. The effects were small in comparison to d amphetamine or methylphenidate. Modafinil substantially increased locomotor activity. The lack of correlation between STR DA efflux and locomotor activity suggests other neurotransmitters have a role in modafinil’s behavioural effects. Financial support: Shire Pharmaceutical Development Ltd. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.532
Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
their non-opioid substance use and multinomial logistic regression was used to predict these substance use groups based on type of opioid drugs used and other characteristics (demographics, pain, treatment history). Results: The most frequently used non-opioid drugs were cannabis (40%), antianxiety medications (34%) and cocaine (25%). LCA identified a 5-class (C) model. C1 (58.7%), had low risk of using non-opioid drugs. C2 (23.5%) had high risk of using anti-anxiety drugs and moderate risk of cannabis. C3 (8.8%) had high risk of using non-opioid prescription drugs (anti-anxiety, sleep, and muscle relaxant drugs) and cannabis. C4 (6.2%) had high risk of using marijuana and cocaine. C5 (2.8%) had high risk of using all nonopioid drugs. Compared to C1 (the low-using group), participants in the other classes were younger, female, tobacco users, had chronic pain, inject opioids, and used both prescription opioids and heroin. The two non-opioid prescription drug groups (C2, C3) were more likely to report chronic pain and use prescription opioids. C4 (marijuana/cocaine users) and C5 (polydrug users) were more likely to report injection. Conclusions: Aggregation of substance use may obscure important subgroup differences in patterns of illicit non-opioid drug use. The identification of two groups that primarily misuse prescription drugs and that have comparatively high rates of chronic pain suggests that self-medication may play a role among sub-groups of OTP patients. Financial support: Denver Health is part of the Researched Abuse Diversion and Addiction-Related Surveillance (RADARS® ) System. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.530 Brief HIV assessment for screening CJ offenders in addiction treatment Grace A. Rowan-Szal, G. Joe, Wayne E. Lehman, N.G. Bartholomew, K. Knight Institute of Behavioral Research, Texas Christian University, Fort Worth, TX, United States Aims: Efficient data collection in high-volume offender drugusing populations has increased demand for assessments that offer diagnostic screening of selective needs. The present study provides psychometric information on a one-page, self-report instrument of 19 items known as the TCU HVHP Form designed to provide information on HIV and hepatitis risks associated with injection drug use, sexual activities, attitudes toward condom use, and health concerns about HIV. In addition, we provide data on the predictive validity of HIV measures completed as part of a Disease Risk Reduction intervention (WaySafe). Methods: Offenders from eight prison-based treatment programs for substance abuse were assessed at intake (N = 1055). The primary instrument was the TCU HVHP along with several background assessments including motivation, psychological functioning, social functioning, and criminal thinking. The TCU WaySafe intervention assessment (administered prior to offenders exiting treatment) included five composite measures: HIV Knowledge Confidence, Avoiding Risky Sex, Avoiding Risky Drug Use, HIV Testing Awareness, and Risk Reduction Skills. Results: Principal components analysis of the HVHP form identified four scales: Injection Risk Behavior, Condom Risk, Sex Risk Behavior, and AIDS Concerns with coefficient alpha reliabilities ranging from .72 to .87. Predictive validities of the scales were demonstrated by their correlations with measures of the WaySafe intervention. The injection risk scale was significantly and negatively correlated with the avoiding risky drug use WaySafe
measure. Correspondingly, the condom risk scale was significantly correlated with the avoiding risky sex WaySafe measure. The HVHP scales had significant correlations with measures of psychological functioning including risk taking, hostility, depression, anxiety, self-esteem and decision making. Conclusions: Findings support use of this brief screening tool to help identify treatment needs in correctional settings. Financial support: Funding was provided by NIDA/NIH through a grant to TCU R01DA025885. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.531 A microdialysis and behavioural investigation of modafinil in freely moving rats H.L. Rowley 1 , R.S. Kulkarni 1 , D. Hackett 2 , David J. Heal 1 1
RenaSci Ltd, Nottingham, United Kingdom Shire Pharmacutical Development Ltd, Basingstoke, United Kingdom 2
Aims: Modafinil is a stimulant used to treat narcolepsy. Its pharmacology is enigmatic, but reports suggest modafinil is a dopamine reuptake inhibitor in human brain in vivo (Volkow et al., 2009, JAMA; 301:1148). Methods: The Culex Bambino automatically collects samples from dual micro-dialysis probes and simultaneously measures locomotor activity in freely moving rats. The effects of modafinil (100, 300 and 600 mg/kg po) on extracellular levels of noradrenaline (NA), dopamine (DA) and 5-HT in prefrontal cortex (PFC) and striatum (STR) and locomotor activity were determined ≤5 h postdosing. Results: No significant (p < 0.05) neurochemical or behavioural changes were produced by modafinil (100 mg/kg po). In PFC, modafinil (300 and 600 mg/kg) produced moderate increases in the efflux of DA (≤214%) and NA (≤263%). The onset of DA efflux was more rapid and peaked earlier (30 min) than NA (105 120 min). In STR, modafinil produced small increases of extracellular DA (≤137%) that were rapid in onset and peaked at 60 min. It had no effect on 5-HT efflux in PFC or STR. Modafinil (300 and 600 mg/kg po) dose-dependently enhanced locomotor activity. At the lower dose, rats were active for ∼2 h, whereas at the higher dose they were active throughout the 5 h experiment. No correlation existed between the increase in STR DA efflux after modafinil (600 mg/kg po) and the degree of locomotor activation (r2 = 0.002; p = 0.857). Conclusions: These data reveal that modafinil enhances neurotransmission by NA and DA in PFC and DA in STR. The effects were small in comparison to d amphetamine or methylphenidate. Modafinil substantially increased locomotor activity. The lack of correlation between STR DA efflux and locomotor activity suggests other neurotransmitters have a role in modafinil’s behavioural effects. Financial support: Shire Pharmaceutical Development Ltd. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.532