Browsing by Subject "Baclofen"

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    Bidirectional enantioselective effects of the GABAB receptor agonist baclofen in two mouse models of excessive ethanol consumption
    (Elsevier, 2015-02) Kasten, Chelsea R.; Blasingame, Shelby N.; Boehm, Stephen L.; Department of Psychology, School of Science
    The GABAB receptor agonist baclofen has been studied extensively in preclinical models of alcohol-use disorders, yet results on its efficacy have been uncertain. Racemic baclofen, which is used clinically, can be broken down into separate enantiomers of the drug. Baclofen has been shown to produce enantioselective effects in behavioral assays, including those modeling reflexive and sexual behavior. The current studies sought to characterize the enantioselective effects of baclofen in two separate models of ethanol consumption. The first was a Drinking-in-the-Dark procedure that provides "binge-like" ethanol access to mice by restricting access to a 2-h period, 3 h into the dark cycle. The second was a two-bottle choice procedure that utilized selectively bred High Alcohol Preferring 1 (HAP1) mice to model chronic ethanol access. HAP1 mice are selectively bred to consume pharmacologically relevant amounts of ethanol in a 24-h two-bottle choice paradigm. The results showed that baclofen yields enantioselective effects on ethanol intake in both models, and that these effects are bidirectional. Total ethanol intake was decreased by R(+)-baclofen, while total intake was increased by S(-)-baclofen in the binge-like and chronic drinking models. Whereas overall binge-like saccharin intake was significantly reduced by R(+)-baclofen, chronic intake was not significantly altered. S(-)-baclofen did not significantly alter saccharin intake. Neither enantiomer significantly affected locomotion during binge-like reinforcer consumption. Collectively, these results demonstrate that baclofen produces enantioselective effects on ethanol consumption. More importantly, the modulation of consumption is bidirectional. The opposing enantioselective effects may explain some of the variance seen in published baclofen literature.
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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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    Intra-nucleus accumbens shell injections of R(+)- and S(-)-baclofen bidirectionally alter binge-like ethanol, but not saccharin, intake in C57Bl/6J mice
    (Elsevier, 2014-10-01) Kasten, Chelsea R.; Boehm II, Stephen L.; Department of Psychology, School of Science
    The GABAB agonist baclofen has been widely researched clinically and preclinically as a treatment of alcohol use disorders (AUDs). However, the efficacy of baclofen remains uncertain. The clinically used racemic compound can be separated into separate enantiomers. These enantiomers have produced different profiles in behavioral assays, with the S- compound often being ineffective compared to the R- compound, or the S- compound antagonizing the effects of the R- compound. We have previously demonstrated that the R(+)-baclofen enantiomer decreases binge-like ethanol intake in the Drinking-in-the-Dark (DID) paradigm, whereas the S(-)-baclofen enantiomer increases ethanol intake. One area implicated in drug abuse is the nucleus accumbens shell (NACsh).The current study sought to define the role of the NACsh in the enantioselective effects of baclofen on binge-like ethanol consumption by directly microinjecting each enantiomer into the structure. Following bilateral cannulation of the NACsh, C57Bl/6J mice were given 5 days of access to ethanol or saccharin for 2h, 3h into the dark cycle. On Day 5 mice were given an injection of aCSF, 0.02 R(+)-, 0.04R(+)-, 0.08 S(-)-, or 0.16 S(-)-baclofen (μg/side dissolved in 200nl of aCSF). It was found that the R(+)-baclofen dose-dependently decreased ethanol consumption, whereas the high S(-)-baclofen dose increased ethanol consumption, compared to the aCSF group. Saccharin consumption was not affected. These results further confirm that GABAB receptors and the NACsh shell are integral in mediating ethanol intake. They also demonstrate that baclofen displays bidirectional, enantioselective effects which are important when considering therapeutic uses of the drug.
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    Intrathecal Baclofen Pump Migration Into the Peritoneal Cavity: A Case Report
    (Kowsar Medical, 2016-06) Kovanda, Timothy J.; Pestereva, Ecaterina; Lee, Albert; Department of Neurological Surgery, IU School of Medicine
    INTRODUCTION: Intrathecal baclofen pumps are valuable treatment options for those with cerebral palsy. Although subfascial baclofen pump placement is generally preferred over a subcutaneous pump placement due to lower infection rates, rare complications can occur with the subfascial approach such as pump migration. CASE PRESENTATION: The authors here describe a case of baclofen pump migration into the peritoneal cavity of a 26-year-old male patient with cerebral palsy, shunted hydrocephalus, and epilepsy. Because the patient's pump could not be palpated on exam and hence refilled, imaging was undertaken, but did not reveal clear evidence of pump migration. Surgery afterward confirmed that the pump had migrated into the peritoneal cavity through a fascial defect. Baclofen pump had to be replaced instead subcutaneously as well as the patient later had to be readmitted for 2 ventriculoperitoneal shunt revisions due to progression of his hydrocephalus. CONCLUSIONS: Intraperitoneal migration of a subfascially placed baclofen pump is a rare, yet serious complication, which has been reported only once in the literature. We advise neurosurgeons to have a low level of threshold in confirming the location of a baclofen pump with imaging and surgical exploration if necessary in order to avoid detrimental outcomes such as bowel perforation.