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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    062—Amphetamine and Related Drugs: Reinforcement, Seeking, and Reinstatement

    Saturday, November 09, 2013, 1:00 pm - 5:00 pm

    62.08: Oxytocin differentially affects the motivation to self-administer methamphetamine in isolated and pair housed female rats

    Location: Halls B-H

    ">*C. WESTENBROEK1, A. N. PERRY1, L. JAGANNATHAN1, J. B. BECKER1,2,3,4;
    1Mol. and Behavioral Neurosci. Inst., Univ. of Michigan, ANN ARBOR, MI; 2Psychology, 3Psychiatry, 4Neurosci. Program, Univ. of Michigan, Ann Arbor, MI

    Abstract Body: Females are more vulnerable to escalation of drug intake than are males, and stress increases drug use. Isolation is a stressor, especially for female rats, and this may contribute to the increased vulnerability in females under standard laboratory testing conditions. The neuropeptide oxytocin (OT) is known for its prosocial and stress-reducing effects. We hypothesized that the positive effects of social housing, previously reported to reduce drug taking behavior, are mediated by OT at the level of dopamine (DA) signaling in the nucleus accumbens shell (NAcSh). Here we investigate the effects of pair-housing and OT on the acute DA response to methamphetamine (METH), and whether there are interactive effects of OT and housing conditions on the motivation to self-administer METH. Female Long-Evans rats were either individually or pair housed for 3 weeks prior to the start of experiment. Animals were fitted with microdialysis guide cannula aimed at the NAcSh and indwelling intravenous catheters for self-administration. The DA response to an acute METH infusion (0.3 mg/kg, i.v.) was investigated. Half of the animals within each housing condition received OT (0.3 mg/kg, i.p.) 30 minutes prior to the METH infusion. The following week animals were trained to self-administer METH (0.06 mg/kg/inf) on a FR1 schedule of reinforcement (max. 15 infusions) for 3 days, after which they were transferred to a progressive ratio schedule for 7 weeks (5 days a week) and breaking point (BP) was used as a measure of motivation. During the last 2 weeks, animals received either saline or OT 30 minutes before self-administration. METH increased DA in the NAcSh in all groups, and pair-housing by itself did not affect the stimulated DA response. However, the METH-induced DA response was higher in isolated OT-treated animals compared to pair-housed OT-treated females. BP increased over time, but to a greater extent in isolated females who had significantly higher BP than pair-housed females after 5 weeks. Two weeks of OT treatment reduced BP in isolated but not pair-housed females. These data show that pair-housing with a non-self administering cage-mate attenuates escalation of the motivation to self-administer METH in female rats, and that chronic OT-treatment reduced motivation for METH in isolated but not pair-housed females. These results indicate that OT may provide a treatment option, especially for individuals with a greater motivation for METH, like isolated females. Future experiments will investigate whether changes in OT mediate the protective effects of social housing.

    Lay Language Summary: We have found that isolation increases the motivation to use the highly addictive psychostimulant methamphetamine in isolated female rats, compared with female rats housed socially. Treatment with the neuropeptide oxytocin, known for its pro-social and stress-reducing properties, decreased motivation for methamphetamine more in the isolated animals, -- indicating that oxytocin could be an effective treatment especially for a more vulnerable population showing a higher level of drug use.
    Addiction to methamphetamine is a major public health concern, however there are no effective pharmacological treatments. The few potential medications that are being tested at the moment for the treatment of psychostimulant addiction appear to be somewhat effective in men but not in women. Our data help illustrate the importance of including females when investigating potential treatments for addiction. Women report a higher exposure to traumatic events and often start using substances to cope with psychological problems. Social bonds have a positive influence on stress-coping and might also have protective effects against addiction and help with recovery. Understanding the underlying mechanisms of social support could lead to new pharmacological targets for treatment of addiction
    We hypothesized that pair housing of female rats, modeling social support, could reduce the motivation for methamphetamine. Additionally we hypothesized that treatment with oxytocin would be an effective in reducing drug-taking behavior and that this would be modulated by the social environment. Female rats were either isolated or housed in pairs, and subjected to 7 weeks of methamphetamine self-administration on a progressive ratio schedule of reinforcement, which forces the rat to work harder for each subsequent infusion. During the last 2 weeks they were treated with oxytocin or received a placebo.
    To our knowledge our study is the first to show positive effects of pair housing on the motivation to take methamphetamine in females, confirming findings in males showing that a positive social environment can reduce drug-taking behavior. Oxytocin has been shown to reduce the motivation to take methamphetamine in male rats, however our study is the first to show a positive effect in female rats that show escalation of drug use.
    Future research will investigate if oxytocin is involved in the protective effects of social housing, and the role of oxytocin in the rewarding effects of methamphetamine and how it modulates reward systems in the brain.
    Women start using methamphetamine at an earlier age and are appear to be more sensitive to its addictive effects than men. In addition women seem more resistant to potential pharmacological treatments. Our results suggest that a positive social environment protects against the addictive effects of methamphetamine, and that oxytocin should be studied as a potential treatment to reduce methamphetamine use in women.

    Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    062—Amphetamine and Related Drugs: Reinforcement, Seeking, and Reinstatement

    Saturday, November 09, 2013, 1:00 pm - 5:00 pm

    62.08: Oxytocin differentially affects the motivation to self-administer methamphetamine in isolated and pair housed female rats

    Location: Halls B-H

    ">*C. WESTENBROEK1, A. N. PERRY1, L. JAGANNATHAN1, J. B. BECKER1,2,3,4;
    1Mol. and Behavioral Neurosci. Inst., Univ. of Michigan, ANN ARBOR, MI; 2Psychology, 3Psychiatry, 4Neurosci. Program, Univ. of Michigan, Ann Arbor, MI

    Abstract Body: Females are more vulnerable to escalation of drug intake than are males, and stress increases drug use. Isolation is a stressor, especially for female rats, and this may contribute to the increased vulnerability in females under standard laboratory testing conditions. The neuropeptide oxytocin (OT) is known for its prosocial and stress-reducing effects. We hypothesized that the positive effects of social housing, previously reported to reduce drug taking behavior, are mediated by OT at the level of dopamine (DA) signaling in the nucleus accumbens shell (NAcSh). Here we investigate the effects of pair-housing and OT on the acute DA response to methamphetamine (METH), and whether there are interactive effects of OT and housing conditions on the motivation to self-administer METH. Female Long-Evans rats were either individually or pair housed for 3 weeks prior to the start of experiment. Animals were fitted with microdialysis guide cannula aimed at the NAcSh and indwelling intravenous catheters for self-administration. The DA response to an acute METH infusion (0.3 mg/kg, i.v.) was investigated. Half of the animals within each housing condition received OT (0.3 mg/kg, i.p.) 30 minutes prior to the METH infusion. The following week animals were trained to self-administer METH (0.06 mg/kg/inf) on a FR1 schedule of reinforcement (max. 15 infusions) for 3 days, after which they were transferred to a progressive ratio schedule for 7 weeks (5 days a week) and breaking point (BP) was used as a measure of motivation. During the last 2 weeks, animals received either saline or OT 30 minutes before self-administration. METH increased DA in the NAcSh in all groups, and pair-housing by itself did not affect the stimulated DA response. However, the METH-induced DA response was higher in isolated OT-treated animals compared to pair-housed OT-treated females. BP increased over time, but to a greater extent in isolated females who had significantly higher BP than pair-housed females after 5 weeks. Two weeks of OT treatment reduced BP in isolated but not pair-housed females. These data show that pair-housing with a non-self administering cage-mate attenuates escalation of the motivation to self-administer METH in female rats, and that chronic OT-treatment reduced motivation for METH in isolated but not pair-housed females. These results indicate that OT may provide a treatment option, especially for individuals with a greater motivation for METH, like isolated females. Future experiments will investigate whether changes in OT mediate the protective effects of social housing.

    Lay Language Summary: We have found that isolation increases the motivation to use the highly addictive psychostimulant methamphetamine in isolated female rats, compared with female rats housed socially. Treatment with the neuropeptide oxytocin, known for its pro-social and stress-reducing properties, decreased motivation for methamphetamine more in the isolated animals, -- indicating that oxytocin could be an effective treatment especially for a more vulnerable population showing a higher level of drug use.
    Addiction to methamphetamine is a major public health concern, however there are no effective pharmacological treatments. The few potential medications that are being tested at the moment for the treatment of psychostimulant addiction appear to be somewhat effective in men but not in women. Our data help illustrate the importance of including females when investigating potential treatments for addiction. Women report a higher exposure to traumatic events and often start using substances to cope with psychological problems. Social bonds have a positive influence on stress-coping and might also have protective effects against addiction and help with recovery. Understanding the underlying mechanisms of social support could lead to new pharmacological targets for treatment of addiction
    We hypothesized that pair housing of female rats, modeling social support, could reduce the motivation for methamphetamine. Additionally we hypothesized that treatment with oxytocin would be an effective in reducing drug-taking behavior and that this would be modulated by the social environment. Female rats were either isolated or housed in pairs, and subjected to 7 weeks of methamphetamine self-administration on a progressive ratio schedule of reinforcement, which forces the rat to work harder for each subsequent infusion. During the last 2 weeks they were treated with oxytocin or received a placebo.
    To our knowledge our study is the first to show positive effects of pair housing on the motivation to take methamphetamine in females, confirming findings in males showing that a positive social environment can reduce drug-taking behavior. Oxytocin has been shown to reduce the motivation to take methamphetamine in male rats, however our study is the first to show a positive effect in female rats that show escalation of drug use.
    Future research will investigate if oxytocin is involved in the protective effects of social housing, and the role of oxytocin in the rewarding effects of methamphetamine and how it modulates reward systems in the brain.
    Women start using methamphetamine at an earlier age and are appear to be more sensitive to its addictive effects than men. In addition women seem more resistant to potential pharmacological treatments. Our results suggest that a positive social environment protects against the addictive effects of methamphetamine, and that oxytocin should be studied as a potential treatment to reduce methamphetamine use in women.