A conditioned taste aversion paradigm was used to determine whether aversion to the pharmacological effects of ethanol, apart from orosensory cues, can contribute to differences in voluntary ethanol consumption in rats of the low-alcohol drinking (UChA) and the high-alcohol drinking (UChB) strains. "Alcohol-naive" UChA and UChB rats were injected intraperitoneally with ethanol (0.5, 1.0, 1.5, or 2.0 g/kg) or saline, paired with consumption of a banana-flavored solution during five conditioning trials. Repeated pairings of banana-flavored solution and ethanol at a dose of 1.5 g/kg produced aversion to the banana-flavored solution in UChA rats, but not in UChB rats, at comparable blood ethanol levels. In addition, the highest dose of ethanol tested (2.0 g/kg) produced stronger aversion to the banana-flavored solution in UChA rats, compared with findings in UChB rats. From these results it is suggested that rats of the UChA strain find the postingestional effects of high-dose ethanol more aversive than do UChB rats. Differences in voluntary ethanol consumption seem to be associated with differences in sensitivity to the aversive effects of ethanol.
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Sci Rep
November 2024
Center for Regenerative Medicine, Faculty of Medicine Clínica Alemana-Universidad del Desarrollo, Avenida Plaza 680, Santiago, Chile.
Alcohol use disorder (AUD) represents a public health crisis with few FDA-approved medications for its treatment. Growing evidence supports the key role of the bidirectional communication between the gut microbiota and the central nervous system (CNS) during the initiation and progression of alcohol use disorder. Among the different protective molecules that could mediate this communication, short chain fatty acids (SCFAs) have emerged as attractive candidates, since these gut microbiota-derived molecules have multi-target effects that could normalize several of the functional and structural parameters altered by chronic alcohol abuse.
View Article and Find Full Text PDFPLoS One
October 2024
Center for Regenerative Medicine, Faculty of Medicine Clínica Alemana-Universidad del Desarrollo, Santiago, Chile.
Background: The treatment of opioid addiction mainly involves the medical administration of methadone or other opioids, aimed at gradually reducing dependence and, consequently, the need for illicit opioid procurement. Thus, initiating opioid maintenance therapy with a lower level of dependence would be advantageous. There is compelling evidence indicating that opioids induce brain oxidative stress and associated glial activation, resulting in the dysregulation of glutamatergic homeostasis, which perpetuates drug intake.
View Article and Find Full Text PDFChronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal-striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances.
View Article and Find Full Text PDFAntioxidants (Basel)
September 2023
Institute of Biomedical Sciences, Faculty of Health Sciences, Universidad Autónoma de Chile, Santiago 8910060, Chile.
High ethanol consumption triggers neuroinflammation, implicated in sustaining chronic alcohol use. This inflammation boosts glutamate, prompting dopamine release in reward centers, driving prolonged drinking and relapse. Fibrate drugs, activating peroxisome proliferator-activated receptor alpha (PPAR-α), counteract neuroinflammation in other contexts, prompting investigation into their impact on ethanol-induced inflammation.
View Article and Find Full Text PDFDrug Alcohol Depend
September 2023
Department of Chemistry, Faculty of Sciences, University of Chile, Santiago 7800003, Chile. Electronic address:
Rationale: Neuronal nicotinic acetylcholine receptors (nAChRs) are implicated in the reinforcing effects of nicotine and ethanol. Previous studies have shown that cytisine and its 5-bromo derivative are partial agonists at the α4β2 nAChRs and that the parent molecule cytisine is effective in reducing both nicotine- and ethanol-self-administration in rats. However, whether 5-bromocytisine affects nicotine or ethanol self-administration was unknown.
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