Browsing by Subject "Propranolol"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
  • Thumbnail Image
    Item
    Greater inhibition of female rat binge alcohol intake by adrenergic receptor blockers using a novel Two-Shot rat binge drinking model
    (Springer Nature, 2024-06-18) De Oliveira Sergio, Thatiane; Smith, Rebecca Jane; Wean, Sarah E.; Engleman, Eric A.; Hopf, Frederic W.; Psychiatry, School of Medicine
    Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-min intake (what we called Two-shot) separated by a 10-min break. Our findings showed during Two-Shot that most animals reached ≥ 80 mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20 to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1 mg/kg), validating intake suppression by a clinical therapeutic agent for human problem drinking. Further, both propranolol (β-adrenergic receptor antagonist) and prazosin (α1-adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.
  • Thumbnail Image
    Item
    Propranolol Elicits Long Term Systemic Effects After Repetitive Mild Traumatic Brain Injury
    (2023-07) Smith, Jared Andre; Obukhov, Alexander; White, Fletcher; Hato, Takashi; Naugle, Kelly; Jin, Xiaoming; Truitt, William; Grimes, Jaison
    There are almost 2 million new traumatic brain injuries (TBIs) every year in the US. Of these, 80% of these can be classified as mild TBI, also known as concussions, that can lead to pronounced long term symptoms months and years after injury. The presence of post traumatic headaches (PTH) is the most common chronic side effect with prevalence of 47-95% of mTBI patients within a week of injury. Though the mechanisms after TBI leading to these headaches and other post mTBI side effects are poorly understood, recent studies have suggested the role of the immune system after injury plays a causal role in this process. Peripheral immune cells can travel to the brain after mTBI as a result of blood brain barrier dysfunction, sympathetic nervous signaling, and the release of inflammatory mediators. Recent studies have shown sympathetic activation after injury can result in IL-10 dependent systemic immunosuppressive state after mTBI. In this study we sought to limit sympathetic dependent immune alterations after injury by injecting the beta blocker propranolol directly after injury and investigating the immune changes in the blood, brain, spleen, and bone marrow of mTBI animals. Together, these data show mTBI causes immune genetic and pathway level changes at least one month after injury and that propranolol alters genes important for metabolism, cytokine signaling, epigenetic modification, innate, and adaptive immunity. We also find that propranolol reduces the presence of Ly6C+ and increases the presence of Ly6C- monocytes in the blood one month after injury; however, it leads to increased Ly6C+ monocyte presence in the spleen of mTBI mice. In conclusion, propranolol administration directly after mTBI leads to immune changes that may lead to long-term improvement in post TBI symptomology.
  • Thumbnail Image
    Item
    The role of beta- and alpha-adrenergic receptors on alcohol drinking
    (Elsevier, 2023) De Oliveira Sergio, Thatiane; Wean, Sarah; Katner, Simon Nicholas; Hopf, Frederic W.; Psychiatry, School of Medicine
    Alcohol Use Disorders (AUD) is characterized by compulsion-like alcohol drinking (CLAD), where intake despite negative consequences can be a major clinical obstacle. With few treatment options available for AUD, there is a significant need for novel therapies. The noradrenergic system is an important hub for regulating stress responses and maladaptive drives for alcohol. Studies have shown that drugs targeting α1 adrenenergic receptors (ARs) may represent a pharmacological treatment for pathological drinking. However, the involvement of β ARs for treating human drinking has received scant investigation, and thus we sought to provide pre-clinical validation for possible AR utility for CLAD by analyzing whether β AR antagonists propranolol (β1/2), betaxolol (β1), and ICI, 118,551 (β2) impacted CLAD and alcohol-only drinking (AOD) in male Wistar rats. We found that the highest dose of propranolol tested systemically (10 mg/kg) reduced alcohol drinking, while 5 mg/kg propranolol reduced drinking with a trend to impact CLAD more than AOD, and with no effects of 2.5 mg/kg. Betaxolol (2.5 mg/kg) also decreased drinking, while ICI 118.551 had no effects. Also, while AR compounds might have utility for AUD, they can also lead to undesirable side effects. Here, a combination of ineffective doses of propranolol and prazosin reduced both CLAD and AOD. Finally, we investigated the effect of propranolol and betaxolol in two brain areas related to pathological drinking, the anterior insula (aINS) and medial prefrontal cortex (mPFC). Surprisingly, propranolol (1-10 μg) in aINS or mPFC did not affect CLAD or AOD. Together, our findings provide new pharmacological insights into noradrenergic regulation of alcohol consumption, which may inform AUD therapy.