Effects of lorazepam tolerance and withdrawal on GABA[sub A] receptor operated chloride channels in mice selected for differences in ethanol withdrawal severity

Journal Article · Wed Jan 01 04:00:00 EST 1992 · Life Sciences; (United States)

DOI:https://doi.org/10.1016/0024-3205(92)90401-A· OSTI ID:6938176

Allan, A M; Baier, L D; Zhang, Xiaoying ^[1]

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1. Washington Univ. School of Medicine, St. Louis, MO (United States)

Withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) mice were treated with 5 mg/kg lorazepam for 7 days via implanted osmotic mini pumps. Following chronic drug treatment, brains were assayed for GABA-mediated chloride flux (GABA-Cl[sup [minus]]). Under control conditions, brain membranes prepared from WSP and WSR lines did not differ in flunitrazepam or ethanol stimulation of GABA-mediated [sup 36]Cl[sup [minus]]uptake, but the WSP lines were more sensitive to inhibition of [sup 36]Cl[sup [minus]] flux by the inverse agonist, FG-7142.. Withdrawal from chronic treatment, by an acute injection with the benzodiazepine antagonist RO15-1788, returned flunitrazepam stimulation of GABA-CL[sup [minus]] to near control levels in WSR membranes but not in WSP membranes and restored ethanol modulation of the channel to control levels in both lines. Inhibition of chloride flux by the benzodiazepine partial inverse agonist, FG-1742 was greater in membranes from WSP mice compared with WSR mice. Tolerance to lorazepam increased sensitivity of the WSR membranes to FG-7142 without altering the response in the WSP line. Again, withdrawal restored the Cl[sup [minus]] flux response to FG-7142 back to near control levels. Lorazepam tolerance lowered [[sup 3]H]-flunitrazepam binding affinity slightly only in the WSR strain with no change in binding number.

• OSTI ID: 6938176
• Journal Information: Life Sciences; (United States), Journal Name: Life Sciences; (United States) Vol. 51:12; ISSN 0024-3205; ISSN LIFSAK
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
AMINO ACIDS
AMINOBUTYRIC ACID
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
BRAIN
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CHLORIDES
CHLORINE 36
CHLORINE COMPOUNDS
CHLORINE ISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ETHANOL
HALIDES
HALOGEN COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
MEMBRANES
MICE
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
PSYCHOTROPIC DRUGS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
TOXICITY
TRACER TECHNIQUES
TRANQUILIZERS
TRITIUM COMPOUNDS
VERTEBRATES
YEARS LIVING RADIOISOTOPES