Browsing by Author "Rodriguez, Eric A."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Neurotoxicity to dopamine neurons after the serial exposure to alcohol and methamphetamine: Protection by COX-2 antagonism
    (Elsevier, 2019) Blaker, Amanda L.; Rodriguez, Eric A.; Yamamoto, Bryan K.; Pharmacology and Toxicology, School of Medicine
    A significant co-morbidity exists between alcohol and methamphetamine (Meth) in humans but the consequences and mechanisms underlying their co-morbid effects remain to be identified. A consequence associated with the abuse of either alcohol or Meth involves inflammation but little is known about the role of inflammation in a possible neurotoxicity arising from their co-exposure. Sprague Dawley rats were allowed 28 days of intermittent, voluntary access to 10% ethanol (EtOH) followed by a neurotoxic binge administration of Meth. EtOH drinking followed by Meth increased microglial cell counts and produced morphological changes in microglia of the substantia nigra pars compacta 2 h after Meth administration that were distinct from those produced by either EtOH or Meth alone. These effects preceded the activation of cleaved caspase-3 in dopamine cell bodies, as well as decreases in tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra and dopamine transporter (DAT) immunoreactivity in the striatum measured at 7 days after Meth. Intervention with a selective COX-2 inhibitor during EtOH drinking prevented the changes in microglia, and attenuated the increase in cleaved caspase-3, and decreases in TH and DAT after Meth administration. Furthermore, motor dysfunction measured by a rotarod test was evident but only in rats that were exposed to both EtOH and Meth. The motor dysfunction was ameliorated by prior inhibition of COX-2 during EtOH drinking. The exaggerated neurochemical and behavioral deficits indicate that the comorbidity of EtOH and Meth induces a degeneration of the nigrostriatal pathway and support the role of inflammation produced by EtOH drinking that primes and mediates the neurotoxic consequences associated with the common co-morbidity of these drugs.
  • Thumbnail Image
    Item
    Toxic Effects of Methamphetamine on Perivascular Health: Co-morbid Effects of Stress and Alcohol Use Disorders
    (Bentham Science, 2021) Rodriguez, Eric A.; Yamamoto, Bryan K.; Pharmacology and Toxicology, School of Medicine
    Methamphetamine (Meth) abuse presents a global problem and commonly occurs with stress and/or alcohol use disorders. Regardless, the biological causes and consequences of these comorbidities are unclear. Whereas the mechanisms of Meth, stress, and alcohol abuse have been examined individually and well-characterized, these processes overlap significantly and can impact the neural and peripheral consequences of Meth. This review focuses on the deleterious cardio- and cerebrovascular effects of Meth, stress, alcohol abuse, and their comorbid effects on the brain and periphery. Points of emphasis are on the composition of the blood-brain barrier and their effects on the heart and vasculature. The autonomic nervous system, inflammation, and oxidative stress are specifically highlighted as common mediators of the toxic consequences to vascular and perivascular health. A significant portion of the Meth abusing population also presents with stress and alcohol use disorders, prompting a need to understand the mechanisms underlying their comorbidities. Little is known about their possible convergent effects. Therefore, the purpose of this critical review is to identify shared mechanisms of Meth, chronic stress, and alcohol abuse that contributes to the dysfunction of vascular health and underscores the need for studies that directly address their interactions.