The Journal of Pharmacology and Experimental Therapeutics
Ethanol is proposed to exert its pharmacological effects by increasing membrane fluidity. Support for this hypothesis comes from strong correlations between in vitro effects of ethanol and pharmacological effects and genetic variation seen in vivo. Because arachidonate acid (AA) cascade is a membrane-bound system activated by disruptions in the cell membrane, it is possible that ethanol-induced membrane fluidization increases the formation of AA metabolites such as prostaglandins.
The influence of gender on the stimulatory and depressant effects of ethanol was examined in C57BL/6 (C57) mice. In Experiment 1, locomotor activity was assessed in young (2-month-old) male and female mice injected intraperitoneally (IP) with stimulatory (1.5 g/kg) or depressant (2.5 g/kg) doses of ethanol. Both the stimulatory and the depressive effects of ethanol were greater in young male than female C57 mice, and the gender difference was unrelated to blood ethanol concentration (BEC).
3-alpha-Hydroxy-5-beta-pregnan-20-one [pregnanolone (PA)] and 3-beta-hydroxy-5-pregnen-20-one 3-sulfate [pregnenolone sulfate (PS)] are steroids that have been shown in biochemical studies to be active at the GABA-benzodiazepine-chloride receptor complex, Pa as a "barbiturate-like" agonist and PS as a "picrotoxin-like" antagonist. Since other compounds that are active at this site interact with the effects of pentobarbital and ethanol, the behavioral effects of these steroids alone and in combination with pentobarbital and ethanol were tested.
In previous studies using Fos expression as a marker of neuronal activation, we showed that nitrous oxide (N(2)O) activates bulbospinal noradrenergic neurons in rats and that destruction of these neuronal pathways leads to loss of N(2)O antinociceptive action. Based on previous rat studies it has been proposed that these noradrenergic neurons are activated through opioid receptors through the release of endogenous opioid ligands in the periaqueductal gray.
BACKGROUND: Acute functional tolerance (AFT) to ethanol-induced hypnosis is one of the main factors that affect the duration of ethanol-induced loss of righting reflex (LRR: "sleep time"). Investigators who use duration of LRR as a measure of ethanol-induced sedation should consider the potential magnitude and time course of this neuroadaptation when interpreting their results. However, AFT to the hypnotic effects of ethanol has not been well characterized. The present study explored this form of AFT using a novel method of monitoring LRR in mice.
Attempts have been made to attribute the particular features of general anaesthesia such as hypnosis, analgesia, amnesia and autonomic stability to certain brain regions. In the present study, we examined the effects of the commonplace volatile anaesthetic isoflurane on synaptic transmission in an in vitro slice preparation of the murine amygdala.
Ketamine is an IV anesthetic with N-methyl-d-aspartate receptor (NMDAR)-blocking properties. However, it is still unclear whether ketamine's general anesthetic actions are mediated primarily via blockade of NMDAR. Functional NMDARs are composed by the assembly of a GluRzeta1 (NR1) subunit with GluRepsilon (GluRepsilon1-4; NR2A-D) subunits, which confer unique properties on native NMDARs. We hypothesized that animals deficient in GluRepsilon1, an abundant and ubiquitously postnatally expressed NMDAR subunit, might be resistant to the effects of ketamine.
Gamma-hydroxybutyrate (GHB), a metabolite of GABA, is a drug of abuse and a therapeutic. The illicit use of GHB precursors and analogs reportedly has increased worldwide. Gamma-hydroxyvaleric (GHV) is a 4-methyl-substituted analog of GHB that reportedly is abused and is marketed as a dietary supplement and replacement for GHB. The purpose of these studies was to compare the pharmacological and behavioral profiles of GHV and GHB.
Propofol (2,6-diisopropylphenol) is a short-acting intravenous anesthetic. Propofol is known to impair maintenance of long-term potentiation (LTP) in synaptic responses from Schaffer collateral-commissural (SC) pathway to CA1 pyramidal cells in the hippocampus, but the threshold concentration of propofol needed to elicit this action is unknown. The actions of propofol in vivo (e.g., amnesia, sedation, hypnosis and immobility) depend on its concentration, and thus it is necessary to determine the concentration required to impair CA1 LTP in order to assess the impact of impairment in vivo.
BACKGROUND: Pharmacogenomics has allowed us to identify the mechanisms underlying much of the inherited variability in drug response. There have been several reports of strain-dependent anesthetic actions in rodents, indicating that significant genetic differences exist in the hypnotic and antinociceptive effects of various anesthetics. METHODS: Loss of righting reflex was used to compare the hypnotic action of pentobarbital, ketamine, nitrous oxide and isoflurane between two genetically different populations of mice, C57BL/6 with black hair and Friends virus B (FVB) with white hair.