The effects of GABA and benzodiazepine receptor antagonists on the anti-conflict actions of diazepam or ethanol

The effects of picrotoxin, bicuculline or RO 15-1788 on the anti-conflict action(s) of diazepam or ethanol were studied in rats using a modified Vogel's conflict test procedure. RO 15-1788 antagonized the anti-punishment effects of diazepam (2.5 mg/kg, IP), whereas various doses of bicuculline or picrotoxin did not interfere with diazepam's anti-conflict effect in this test situation. The anti-conflict action of ethanol (2 g/kg, IP) was antagonized by picrotoxin (1.0 mg/kg, IP), whereas both bicuculline and RO 15-1788 were without effect on the increased punishment response produced by ethanol. These data suggest that the anti-conflict properties of ethanol are at least partially mediated through an enhancement of central GABAergic activity.

[1]  M. Ticku,et al.  Alterations in γ‐Aminobutyric Acid Receptor Sensitivity Following Acute and Chronic Ethanol Treatments , 1980, Journal of neurochemistry.

[2]  E. Petersen,et al.  Sodium valproate exerts anti-conflict activity in rats without any concomitant rise in forebrain GABA level. , 1981, Life sciences.

[3]  L. Pieri,et al.  Selective antagonists of benzodiazepines , 1981, Nature.

[4]  A. Turner,et al.  Biochemical dissection of the γ-aminobutyrate synapse , 1983 .

[5]  F. Bloom,et al.  Effects of naloxone on the anticonflict properties of alcohol and chlordiazepoxide. , 1980, Substance and alcohol actions/misuse.

[6]  R. Olsen,et al.  gamma-Aminobutyric acid-stimulated chloride permeability in crayfish muscle. , 1977, Biochimica et biophysica acta.

[7]  J. Nestoros.  Ethanol specifically potentiates GABA-mediated neurotransmission in feline cerebral cortex. , 1980, Science.

[8]  A. Jobert,et al.  Conditioned suppression of behavior: Its reversal by intra raphe microinjection of chlordiazepoxide and GABA , 1980, Neuroscience Letters.

[9]  L. Cook,et al.  Behavioral Pharmacology of Antianxiety Drugs , 1978 .

[10]  R. A. Davidoff,et al.  Alcohol and presynaptic inhibition in an isolated spinal cord preparation. , 1973, Archives of neurology.

[11]  A. Guidotti,et al.  Specific proconvulsant action of an imidazobenzodiazepine (RO 15-1788) on isoniazid convulsions , 1982, Neuropharmacology.

[12]  L. Pohorecky,et al.  Ethanol and the response to electric shock in rats. , 1976, Life sciences.

[13]  G. Breese,et al.  GABAergic modulation of ethanol-induced motor impairment. , 1982, The Journal of pharmacology and experimental therapeutics.

[14]  A. Guidotti,et al.  Molecular mechanisms in the receptor action of benzodiazepines. , 1979, Annual review of pharmacology and toxicology.

[15]  J. Rossier,et al.  Anxiogenic and non-anxiogenic benzodiazepine antagonists , 1983, Nature.

[16]  S H Snyder,et al.  GABA receptors are increased in brains of alcoholics , 1981, Annals of neurology.

[17]  R. Olsen.  GABA‐Benzodiazepine‐Barbiturate Receptor Interactions , 1981, Journal of neurochemistry.

[18]  S. Parmar,et al.  Anti-inflammatory, antiproteolytic, and antihemolytic properties of pyrrole carboxylic acids. , 1981, Pharmacology.

[19]  M. Ticku,et al.  Ethanol enhances [3H]diazepam binding at the benzodiazepine-gamma-aminobutyric acid receptor-ionophore complex. , 1981, Molecular Pharmacology.

[20]  H. Yamamura,et al.  An allosteric model for benzodiazepine receptor function. , 1983, Biochemical pharmacology.

[21]  R. Harris,et al.  Behavioral evidence for the involvement of γ-aminobutyric acid in the actions of ethanol , 1983 .

[22]  A. Guidotti,et al.  Potentiation by intraventricular muscimol of the anticonflict effect of benzodiazepines , 1980, Brain Research.

[23]  C. Gardner,et al.  Effects of agents which enhance GABA-mediated neurotransmission on licking conflict in rats and exploration in mice. , 1982, European journal of pharmacology.

[24]  B. Beer,et al.  The separation of 3H-Benzodiazepine binding sites in brain and of benzodiazepine pharmacological properties , 1983, Pharmacology Biochemistry and Behavior.

[25]  L. Stein,et al.  Benzodiazepines: behavioral and neurochemical mechanisms. , 1977, The American journal of psychiatry.

[26]  M. Ticku,et al.  The interactions of ethanol with the benzodiazepine-GABA receptor-ionophore complex , 1983, Pharmacology Biochemistry and Behavior.

[27]  L. Cook,et al.  Mechanism of action of the benzodiazepines: behavioral aspect. , 1980, Federation proceedings.

[28]  M. Billingsley,et al.  The effects of naloxone and picrotoxin on the sedative and anticonflict effects of benzodiazepines. , 1978, Life sciences.

[29]  Leander Jd,et al.  Drugs and punished responding. V. Effects of drugs on responding suppressed by response-dependent and response-independent electric shock. , 1975 .

[30]  P. Cowen,et al.  Unusual interactions of benzodiazepine receptor antagonists , 1982, Nature.

[31]  E. Costa.  Benzodiazepines and neurotransmitters. , 1980, Arzneimittel-Forschung.