Related Experiment Video

Updated: Sep 20, 2026

Modeling Alcohol Consumption in Rodents Using Two-Bottle Choice Home Cage Drinking and Microstructural Analysis
08:45

Modeling Alcohol Consumption in Rodents Using Two-Bottle Choice Home Cage Drinking and Microstructural Analysis

Published on: November 8, 2024

Influence of drugs acting on nitric oxide-dependent pathways on ethanol tolerance in rats

Elisabeth Wazlawik1, Gina Struffaldi Morato

  • 1Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Rua Ferreira Lima 82, 88015-420 Florianopolis, Santa Catarina, Brazil.

Psychopharmacology
|September 5, 2003
PubMed
Abstract

Insights

Nitric oxide (NO) pathways influence ethanol tolerance. Inhibiting soluble guanylyl cyclase (sGC) blocked tolerance, while NO donors and cGMP analogs enhanced it, supporting NO's role in brain ethanol tolerance development.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Previous research indicates nitric oxide (NO) synthesis inhibition blocks ethanol tolerance.
  • Investigating NO-dependent pathways is crucial for understanding ethanol's effects.

Purpose of the Study:

  • To explore the role of NO-dependent pathways in developing tolerance to ethanol's incoordinating effects.
  • To examine how activating or inhibiting NO pathways impacts ethanol tolerance.

Main Methods:

  • Rats received ICV injections of sGC inhibitors (methylene blue, LY83583, ODQ, NS2028) or controls.
  • Tolerance was assessed using the tilt plane apparatus 24 hours after initial ethanol exposure.
  • Effects of NO donors (SNAP, SNP) and a cGMP analog (8-bromo-cGMP) were also evaluated.

Main Results:

  • Soluble guanylyl cyclase (sGC) inhibitors significantly inhibited rapid ethanol tolerance.
  • Sodium nitroprusside (SNP) and 8-bromo-cGMP administration increased the magnitude of ethanol tolerance.

Conclusions:

  • NO-dependent pathway activation or inhibition modulates rapid ethanol tolerance.
  • Brain NO plays a significant role in ethanol tolerance, warranting further investigation into shared cellular mechanisms.

More Related Videos

Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder05:12

Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder

Published on: June 23, 2023

Flypub To Study Ethanol Induced Behavioral Disinhibition and Sensitization08:13

Flypub To Study Ethanol Induced Behavioral Disinhibition and Sensitization

Published on: May 18, 2020

Related Concept Videos

CNS Depressants: Alcohol and Nicotine01:27

CNS Depressants: Alcohol and Nicotine

Ethanol, a clear colorless alcohol, has been consumed by humans for millennia, but its effects on the body are far from benign. At lower doses, it induces decreased inhibitions and loquaciousness, leading to its social appeal. However, it can cause severe consequences at higher doses, such as coma and respiratory depression, due to its zero-order elimination kinetics. Chronic ethanol abuse wreaks havoc on multiple organ systems, particularly the CNS and the liver. Abrupt cessation of ethanol...
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
Drug toxicity: Drug–Drug Interaction01:30

Drug toxicity: Drug–Drug Interaction

Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...