Browsing by Subject "Self-administration"

Now showing 1 - 8 of 8
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    Developing a model of limited-access nicotine consumption in C57Bl/6J mice
    (Elsevier, 2016-09) Kasten, C.R.; Frazee, A.M.; Boehm, S.L.; Psychology, School of Science
    Although United States smoking rates have been on the decline over the past few decades, cigarette smoking still poses a critical health and economic threat. Very few treatment options for smoking exist, and many of them do not lead to long-term abstinence. Preclinical models are necessary for understanding the effects of nicotine and developing treatments. Current self-administration models of nicotine intake may require surgical procedures and often result in low levels of intake. Further, they do not lend themselves to investigating treatments. The current study sought to develop a limited-access model of nicotine intake using the Drinking-in-the-Dark paradigm, which results in high levels of binge-like ethanol consumption that can be pharmacologically manipulated. The present study found that mice will consume nicotine under a range of parameters. Intakes under the preferred condition of 0.14 mg/ml nicotine in 0.2% saccharin reached over 6 mg/kg in two hours and were reduced by an injection of R(+)-baclofen. Mecamylamine did not significantly affect nicotine consumption. As nicotine and ethanol are often co-abused, nicotine intake was also tested in the presence of ethanol. When presented in the same bottle, mice altered nicotine intake under various concentrations to maintain consistent levels of ethanol intake. When nicotine and ethanol were presented in separate bottles, mice greatly reduced their nicotine intake while maintaining ethanol intake. In conclusion, these studies characterize a novel model of limited-access nicotine intake that can be pharmacologically manipulated.
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    Drinking Rhythms in Alcohol Preferring Mice
    (2012-08-29) Matson, Liana M.; Grahame, Nicholas J.; Czachowski, Cristine; Boehm II, Stephen L.
    Multiple lines of High Alcohol Preferring (HAP) mice were selectively bred for their intake of 10% ethanol (v/v) during 24-h daily access over a four-week period, with the highest drinking lines exhibiting intakes in excess of 20 g/kg/day. Drinking rhythms and corresponding blood ethanol concentrations (BEC) of the highest drinking HAP lines to those of the C57BL/6J (B6) inbred strain. Adult male and female crossed HAP (cHAP), HAP1 and B6 mice had free-choice access to 10% ethanol and water for 3 weeks prior to bi-hourly assessments of intake throughout the dark portion of a reverse 12:12 light dark cycle. In another cohort of cHAP mice, the same procedure was used to assess bi-hourly ethanol intake, and blood samples were taken across the day to look at the pattern of accumulation in these mice. Finally, considering the high level of intake by cHAP mice, we were interested in assessing whether metabolic and functional tolerance develop following chronic free-choice access, which were assessed using 2.0 and 1.75 g/kg challenge doses of 20% ethanol, respectively. cHAP and HAP1 mice maintained an excessive level of intake throughout the dark portion of the cycle, accumulating mean BEC levels of 261.5 + 18.09 and 217.9 + 25.02 mg/dl at 7-8 hours following lights off, respectively. B6 mice drank comparatively modestly, and did not accumulate high BEC levels (53.63 + 8.15 mg/dl). In the cHAP cohort, mean BECs were 112.47 + 19.91 at 2 hours after lights off, 189.00 + 27.40 at 6 hours after lights off, 193.80 + 29.66 at 10 hours after lights off, and 89.68 + 22.19 at 2 hours after lights on. Further, following 3 weeks of ethanol access, cHAP mice had a faster rate of ethanol metabolism and fewer hind slips than water-only exposed mice (ps < .05). In conclusion, the excessive free-choice drinking demonstrated by the HAP1 and cHAP lines, as well as the pattern of sustained high BECs in cHAP mice, challenge the notion that rodents will not reliably and voluntarily sustain ethanol intake at pharmacologically relevant levels. These results suggest that the highest drinking HAP lines may provide a unique opportunity for modeling the excessive intake that has been observed in alcohol-dependent individuals. Further, we observed that cHAP mice develop both metabolic and functional tolerance to the ataxic effects of ethanol following 3 weeks of free-choice access. Together, these findings support HAP mice as translational rodent model of alcoholism, and provide rationale for exploration of the predisposing factors for excessive consumption, as well as the development of physiological, behavioral, and toxicological outcomes following alcohol exposure.
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    The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption
    (Society for Neuroscience, 2003-03) Bachtell, Ryan K.; Weitemier, Adam Z.; Galvan-Rosas, Agustin; Tsivkovskaia, Natalia O.; Risinger, Fred O.; Phillips, Tamara J.; Grahame, Nicholas J.; Ryabinin, Andrey E.; Psychiatry, School of Medicine
    Identifying and characterizing brain regions regulating alcohol consumption is beneficial for understanding the mechanisms of alcoholism. To this aim, we first identified brain regions changing in expression of the inducible transcription factor c-Fos in the alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) mice after ethanol consumption. Drinking a 5% ethanol/10% sucrose solution in a 30 min limited access procedure led to induction of c-Fos immunoreactivity in urocortin (Ucn)-positive cells of the Edinger-Westphal nucleus (EW), suppression of c-Fos immunoreactivity in the dorsal portion of the lateral septum (LS) of both strains of mice, and strain-specific suppression in the intermediate portion of the LS and the CA3 hippocampal region. Because the EW sends Ucn projections to the LS, and B6 and D2 mice differ dramatically in EW Ucn expression, we further analyzed the Ucn EW–LS pathway using several genetic approaches. We find that D2 mice have higher numbers of Ucn-immunoreactive processes than B6 mice in the LS and that consumption of ethanol/sucrose in the F2 offspring of a B6D2 intercross positively correlates with Ucn immunoreactivity in the EW and negatively correlates with Ucn immunoreactivity in the LS. In agreement with these findings, we find that alcohol-avoiding male B6.D2Alcp1 line 2.2 congenic mice have lower Ucn immunoreactivity in the EW than male B6.B6 mice. Finally, we also find that HAP mice, selectively bred for high alcohol preference, have higher Ucn immunoreactivity in EW, than LAP mice, selectively bred for low alcohol preference. Taken together, these studies provide substantial evidence for involvement of the EW–LS Ucn pathway in alcohol consumption.
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    Medication management strategies used by older adults with heart failure: A systems-based analysis
    (Oxford Academic, 2018-06) Mickelson, Robin S.; Holden, Richard J.; BioHealth Informatics, School of Informatics and Computing
    Background: Older adults with heart failure use strategies to cope with the constraining barriers impeding medication management. Strategies are behavioral adaptations that allow goal achievement despite these constraining conditions. When strategies do not exist, are ineffective or maladaptive, medication performance and health outcomes are at risk. While constraints to medication adherence are described in literature, strategies used by patients to manage medications are less well-described or understood. Aim: Guided by cognitive engineering concepts, the aim of this study was to describe and analyze the strategies used by older adults with heart failure to achieve their medication management goals. Methods: This mixed methods study employed an empirical strategies analysis method to elicit medication management strategies used by older adults with heart failure. Observation and interview data collected from 61 older adults with heart failure and 31 caregivers were analyzed using qualitative content analysis to derive categories, patterns and themes within and across cases. Results: Data derived thematic sub-categories described planned and ad hoc methods of strategic adaptations. Stable strategies proactively adjusted the medication management process, environment, or the patients themselves. Patients applied situational strategies (planned or ad hoc) to irregular or unexpected situations. Medication non-adherence was a strategy employed when life goals conflicted with medication adherence. The health system was a source of constraints without providing commensurate strategies. Conclusions: Patients strived to control their medication system and achieve goals using adaptive strategies. Future patient self-mangement research can benefit from methods and theories used to study professional work, such as strategies analysis.
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    Offspring of parents with an alcohol use disorder prefer higher levels of brain alcohol exposure in laboratory experiments involving computer-assisted self-infusion of ethanol (CASE)
    (SpringerLink, 2009-03) Zimmermann, Ulrich S.; Mick, Inge; Laucht, Manfred; Vitvitskiy, Victor; Plawecki, Martin H.; Mann, Karl F.; O’Connor, Sean; Psychiatry, School of Medicine
    Rationale: Acute alcohol effects may differ in social drinkers with a positive family history of alcohol use disorders (FHP) compared to FH negative (FHN) controls. Objectives: To investigate whether FHP subjects prefer higher levels of brain alcohol exposure than do FHN controls. Materials and methods: Twenty-two young healthy nondependent social drinkers participated in two identical sessions of computer-assisted self-infusion of ethanol (CASE); the first for practicing the procedures, the second to test hypotheses. All 12 FHP (four women) and ten FHN (three women) participants received a priming exposure, increasing arterial blood alcohol concentration (aBAC) to 30 mg% at 10 min and decreasing it to 15 mg% at 25 min. A 2-h self-administration period followed, during which only the subjects could increase their aBAC by pressing a button connected to a computer controlling the infusion pump. Infusion rate profiles were calculated instantaneously to increase aBAC by precisely 7.5 mg% within 2.5 min after each button press, followed by a steady descent. Subjects were instructed to produce the same alcohol effects as they would do at a weekend party. Results: The mean and maximum aBAC during the self-administration period and the number of alcohol requests (NOAR) were significantly higher in the FHP vs. FHN participants. Conclusions: This is the first laboratory experiment demonstrating higher alcohol self-administration in FHP compared to FHN subjects. A practice session increases the sensitivity of CASE experiments for detection of subtle differences in human alcohol self-administration.
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    The reinforcing properties of ethanol are quantitatively enhanced in adulthood by peri-adolescent ethanol, but not saccharin, consumption in female alcohol-preferring (P) rats
    (Elsevier, 2015-08) Toalston, Jamie E.; Deehan Jr., Gerald A.; Hauser, Sheketha R.; Engleman, Eric A.; Bell, Richard L.; Murphy, James M.; McBride, William J.; Rodd, Zachary A.; Department of Psychiatry, IU School of Medicine
    Alcohol drinking during adolescence is associated in adulthood with heavier alcohol drinking and an increased rate of alcohol dependence. Past research in our laboratory has indicated that peri-adolescent ethanol consumption can enhance the acquisition and reduce the rate of extinction of ethanol self-administration in adulthood. Caveats of the past research include reinforcer specificity, increased oral consumption during peri-adolescence, and a lack of quantitative assessment of the reinforcing properties of ethanol. The current experiments were designed to determine the effects of peri-adolescent ethanol or saccharin drinking on acquisition and extinction of oral ethanol self-administration and ethanol seeking, and to quantitatively assess the reinforcing properties of ethanol (progressive ratio). Ethanol or saccharin access by alcohol-preferring (P) rats occurred during postnatal day (PND) 30-60. Animals began operant self-administration of ethanol or saccharin after PND 85. After 10 weeks of daily operant self-administration, rats were tested in a progressive ratio paradigm. Two weeks later, self-administration was extinguished in all rats. Peri-adolescent ethanol consumption specifically enhanced the acquisition of ethanol self-administration, reduced the rate of extinction for ethanol self-administration, and quantitatively increased the reinforcing properties of ethanol during adulthood. Peri-adolescent saccharin consumption was without effect. The data indicate that ethanol consumption during peri-adolescence results in neuroadaptations that may specifically enhance the reinforcing properties of ethanol during adulthood. This increase in the reinforcing properties of ethanol could be a part of biological sequelae that are the basis for the effects of adolescent alcohol consumption on the increase in the rate of alcoholism during adulthood.
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    Roflumilast Treatment During Forced Abstinence Reduces Relapse to Methamphetamine Seeking and Taking
    (Wiley, 2022) Baek, James J.; Kline, Hannah; Deveau, Carmen M.; Yamamoto, Bryan K.; Pharmacology and Toxicology, School of Medicine
    Methamphetamine (METH) is a psychostimulant with high abuse potential. Currently there are no pharmacological treatments specific for METH abuse or stimulant use disorder generally. Although phosphodiesterase inhibitors have shown some promise, current animal models have not examined their use in abstinence from stimulant abuse. We employed a METH self-administration model in the rat followed by a forced abstinence period during which roflumilast, a phosphodiesterase 4 inhibitor, was administered. A detailed behavioral analysis of chronic treatment with roflumilast during 7 days of forced abstinence showed that roflumilast reduced METH seeking and METH taking upon subsequent relapse test. Roflumilast treatment during 7 days of forced abstinence did not affect sucrose seeking and sucrose taking behaviors. These data suggest that roflumilast may be a treatment for METH use disorder that is effective when administered only during abstinence.
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    The involvement of mesolimbic dopamine system in cotinine self-administration in rats
    (Elsevier, 2022) Tan, Xiaoying; Ingraham, Cynthia M.; McBride, William J.; Ding, Zheng-Ming; Psychiatry, School of Medicine
    Cotinine is the major metabolite of nicotine and has recently been shown to be self-administered intravenously by rats. However, mechanisms underlying cotinine self-administration remained unknown. Mesolimbic dopamine system projecting from the ventral tegmental area (VTA) to nucleus accumbens (NAC) is closely implicated in drug reinforcement, including nicotine. The objective of the current study was to determine potential involvement of mesolimbic dopamine system in cotinine self-administration. An intracranial self-administration experiment demonstrates that cotinine at 0.88 and 1.76 ng/100 nl/infusion was self-infused into the VTA by rats. Rats produced more infusions of cotinine than vehicle and responded more on active than inactive lever during acquisition, reduced responding when cotinine was replaced by vehicle, and resumed responding during re-exposure to cotinine. Microinjection of cotinine at 1.76 ng/100 nl/infusion into the VTA increased extracellular dopamine levels within the NAC. Subcutaneous injection of cotinine at 1 mg/kg also increased extracellular dopamine levels within the NAC. Administration of the D1-like receptor antagonist SCH 23390 attenuated intravenous cotinine self-administration. On the other hand, bupropion, a catecholamine uptake inhibitor, did not significantly alter intravenous cotinine self-administration. These results suggest that activation of mesolimbic dopamine system may represent one cellular mechanism underlying cotinine self-administration. This shared mechanism between cotinine and nicotine suggests that cotinine may play a role in nicotine reinforcement.