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Browsing by Subject "Alcohol-preferring (P) rats"
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Item Regulation of the Deleterious Effects of Binge-Like Exposure to Alcohol during Adolescence by α7 Nicotinic Acetylcholine Receptor Agents: Prevention by Pretreatment with a α7 Negative Allosteric Modulator and Emulation by a α7 Agonist in Alcohol-Preferring (P) Male and Female Rats(SpringerLink, 2020-09) Rodd, Zachary A.; Hauser, Sheketha R.; Swartzwelder, H. Scott; Waeiss, R. Aaron; Lahiri, Debomoy K.; Bell, Richard L.; Psychiatry, School of MedicineRationale and objectives: Binge-like alcohol consumption during adolescence associates with several deleterious consequences during adulthood including an increased risk for developing alcohol use disorder (AUD) and other addictions. Replicated preclinical data has indicated that adolescent exposure to binge-like levels of alcohol results in a reduction of choline acetyltransferase (ChAT) and an upregulation in the α7 nicotinic receptor (α7). From this information, we hypothesized that the α7 plays a critical role in mediating the effects of adolescent alcohol exposure. Methods: Male and female P rats were injected with the α7 agonist AR-R17779 (AR) once during 6 time points between post-natal days (PND) 29-37. Separate groups were injected with the α7 negative allosteric modulator (NAM) dehydronorketamine (DHNK) 2 h before administration of 4 g/kg EtOH (14 total exposures) during PND 28-48. On PND 75, all rats were given access to water and ethanol (15 and 30%) for 6 consecutive weeks (acquisition). All rats were then deprived of EtOH for 2 weeks and then, alcohol was returned (relapse). Results: Administration of AR during adolescence significantly increased acquisition of alcohol consumption during adulthood and prolonged relapse drinking in P rats. In contrast, administration of DHNK prior to binge-like EtOH exposure during adolescence prevented the increase in alcohol consumption observed during acquisition of alcohol consumption and the enhancement of relapse drinking observed during adulthood. Discussion: The data indicate that α7 mediates the effects of alcohol during adolescence. The data also indicate that α7 NAMs are potential prophylactic agents to reduce the deleterious effects of adolescent alcohol abuse.Item Therapeutic challenges for concurrent ethanol and nicotine consumption: naltrexone and varenicline fail to alter simultaneous ethanol and nicotine intake by female alcohol-preferring (P) rats(Springer, 2019-02-13) Waeiss, Robert A.; Knight, Christopher P.; Hauser, Sheketha R.; Pratt, Lauren A.; McBride, William J.; Rodd, Zachary A.; Psychiatry, School of MedicineRationale and Objectives: Simultaneous alcohol and nicotine consumption occurs in the majority of individuals with alcohol use disorder (AUD) and nicotine dependence. Varenicline (Var) is used to assist in the cessation of nicotine use, while naltrexone (Nal) is the standard treatment for AUD. Despite evidence that ethanol (EtOH) and nicotine (NIC) co-use produces unique neuroadaptations, preclinical research has focused on the effects of pharmacotherapeutics on a single reinforcer. The current experiments examined the effects of Var and Nal on EtOH, NIC, or EtOH+NIC intake. Methods: Animals were randomly assigned to 1 of 4 drinking conditions of 24-hour access to a 3-bottle choice paradigm, one of which always contained water. Drinking conditions were water only, 0.07 and 0.14 mg/mL NIC (NIC only), 15% and 30% EtOH (EtOH only), or 15% and 30% EtOH with 0.14 mg/mL NIC (EtOH+NIC). The effects of Var (0, 1, or 2 mg/kg) or Nal (0, 1, or 10 mg/kg) injections on maintenance and relapse consumption were determined during 4 consecutive days. Results: Var reduced maintenance and relapse NIC intake but had no effect on EtOH or EtOH+NIC drinking. Conversely, Nal reduced EtOH maintenance and relapse drinking, but had no effect on NIC or EtOH+NIC drinking. Discussion: The results indicate the standard pharmacological treatments for nicotine dependence and AUD were effective at reducing consumption of the targeted reinforcer but neither reduced EtOH+NIC couse/abuse. These findings suggest that co-abuse may promote unique neuroadaptations that require models of polysubstance abuse to develop pharmacotherapeutics to treat AUD and nicotine dependence.