Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines

doi:10.1016/0091-3057(80)90067-2

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Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines

Journal Article•DOI•

Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines

Jacqueline N. Crawley, Frederick K. Goodwin

01 Aug 1980-Pharmacology, Biochemistry and Behavior (PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR)-Vol. 13, Iss: 2, pp 167-170

TL;DR: The increased exploratory activity with benzodiazepines does not appear to be a non-specific increase in general motor activity, as locomotion in clonazepam and chlordiazepoxide treated mice placed in a bare, undifferentiated cage was not significantly different from vehicle treated mice.

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Abstract: A simple system is described to analyze the possibility that increased exploratory behavior is an index for the anxiolytic effects of benzodiazepines in laboratory rodents. Mice were allowed free run in a two-chambered arena, where two-thirds of the area was illuminated and one-third was darkened. The two chambers were separated by a black partition equipped with photocells across the opening, and the entire cage rested on an Animex activity monitor. Transitions across the partition between the light and dark chambers, and total Animex locomotor activity, were increased by clonazepam and chlordiazepoxide, in dose-dependent ranges consistent with previously reported behavior models. The increased exploratory activity with benzodiazepines does not appear to be a non-specific increase in general motor activity, as locomotion in clonazepam and chlordiazepoxide treated mice placed in a bare, undifferentiated cage was not significantly different from vehicle treated mice.

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Journal Article•DOI•

Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies.

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Jacqueline N. Crawley¹, John K. Belknap², Allan C. Collins³, John C. Crabbe², Wayne N. Frankel, Norman D. Henderson⁴, Robert Hitzemann⁵, Stephen C. Maxson⁶, Lucinda L. Miner¹, Alcino J. Silva⁷, Jeanne M. Wehner³, Anthony Wynshaw-Boris, Richard Paylor¹ - Show less +9 more•Institutions (7)

National Institutes of Health¹, Oregon Health & Science University², University of Colorado Boulder³, Oberlin College⁴, Stony Brook University⁵, University of Connecticut⁶, Cold Spring Harbor Laboratory⁷

29 Jun 1997-Psychopharmacology

TL;DR: Strain distributions are described for open field activity, learning and memory tasks, aggression, sexual and parental behaviors, acoustic startle and prepulse inhibition, and the behavioral actions of ethanol, nicotine, cocaine, opiates, antipsychotics, and anxiolytics.

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Abstract: Choosing the best genetic strains of mice for developing a new knockout or transgenic mouse requires extensive knowledge of the endogenous traits of inbred strains. Background genes from the parental strains may interact with the mutated gene, in a manner which could severely compromise the interpretation of the mutant phenotype. The present overview summarizes the literature on a wide variety of behavioral traits for the 129, C57BL/6, DBA/2, and many other inbred strains of mice. Strain distributions are described for open field activity, learning and memory tasks, aggression, sexual and parental behaviors, acoustic startle and prepulse inhibition, and the behavioral actions of ethanol, nicotine, cocaine, opiates, antipsychotics, and anxiolytics. Using the referenced information, molecular geneticists can choose optimal parental strains of mice, and perhaps develop new embryonic stem cell progenitors, for new knockouts and transgenics to investigate gene function, and to serve as animal models in the development of novel therapeutics for human genetic diseases.

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1,363 citations

Cites background from "Preliminary report of a simple anim..."

...…of the light↔dark model has shown that anxiolytic drugs increase exploratory behaviors, as measured by the number of transitions and/or time spent in the dark, while other classes of drugs do not (Crawley and Goodwin 1980; Crawley 1981; Crawley et al. 1981, 1986; Mathis et al. 1994, 1995 )....
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...The mouse light↔dark exploration model of anxietyrelated behaviors is based on the ethologically-relevant conflict between the tendency of mice to explore a novel environment, and the aversive properties of a brightly lit open field (Crawley and Goodwin 1980; Crawley 1981)....
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Journal Article•DOI•

The mouse light/dark box test.

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Michel Bourin, Martine Hascoët

28 Feb 2003-European Journal of Pharmacology

TL;DR: The light/dark test may be useful to predict anxiolytic-like or anxiogenic-like activity in mice, and has the advantages of being quick and easy to use, without requiring the prior training of animals.

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1,177 citations

Cites background or methods from "Preliminary report of a simple anim..."

...W (400 lx) Table 1 The main different light/dark procedures used References Crawley and Goodwin, 1980; Crawley and Davis, 1982; Crawley et al., 1983; Crawley et al., 1984, 1997 Costall et al., 1988a,b, 1989, 1990, 1991, 1993 Gao and Cutler, 1992 Belzung et al., 1987, 1994 Hascoët and Bourin et al., 1996; Hascoët and Bourin, 1998; Hascoët et al., 1999, 2000a,b Shimada et al., 1995 Young and Johnson, 1988, 1991a,b Size of 44 21 21 45 27 27 31 46 (dark) 20 20 14 46 27 30 corridor-type 40 33 20 (dark) boxes (cm) 1/3 dark 2/3 light 2/5 dark 3/5 light 60 46 (light) 1/2 dark 1/2 light tunnel between the two compartments 1/3 dark 2/3 light runway two compartments diagonally placed on corner 42 42 20 (light) Light/dark cycle normal inversed inversed inversed normal normal 4 h of dark before testing Compartment where mice are placed in the light in the light in the light in the light in the light in the corner in the light Duration of the test 10 min 5 min 5 min 5 min 5 min 3 min 10 min Parameters used Latency time + + + Transitions + + + + + + Movements in the light + + + + + + Movements in the dark + + + + + + Time in the light + + + + + + + Time in the dark + + + + + + + Rears + + + + ‘‘ + ’’ parameters used by authors considered. light source....
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...In the procedures of Crawley and Goodwin (1980) and Costall et al. (1989), faeces are removed after a trial and urine is wiped up and the box is cleaned with water....
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...The light/dark test is based on the innate aversion of rodents to brightly illuminated areas and on the spontaneous exploratory behaviour of rodents in response to mild stressors, that is, novel environment and light (Crawley and Goodwin, 1980)....
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...W (400 lx) Table 1 The main different light/dark procedures used References Crawley and Goodwin, 1980; Crawley and Davis, 1982; Crawley et al., 1983; Crawley et al., 1984, 1997 Costall et al., 1988a,b, 1989, 1990, 1991, 1993 Gao and Cutler, 1992 Belzung et al., 1987, 1994 Hascoët and Bourin et…...
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...Crawley and Goodwin (1980) described a model in which benzodiazepines produced a facilitation of exploratory behaviour between an illuminated open field and a dark enclosure....
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Journal Article•DOI•

Fmr1 knockout mice: A model to study fragile X mental retardation

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Cathy E. Bakker¹, C. Verheij¹, Rob Willemsen¹, Robert van der Helm¹, Frank Oerlemans², M. Vermey¹, Anne E. Bygrave³, A. T. Hoogeveen¹, Ben A. Oostra¹, Edwin Reyniers⁴, Kristel De Boule⁴, Rudi D'Hooge⁴, Patrick Cras⁴, Désiré van Velzen⁴, Guy Nagels⁴, Jean-Jacques Martin⁴, Peter Paul De Deyn⁴, John K. Darby⁴, Patrick Willems⁴ - Show less +15 more•Institutions (4)

Erasmus University Rotterdam¹, Radboud University Nijmegen², National Institute for Medical Research³, University of Antwerp⁴

15 Jul 1994-Cell

TL;DR: In this article, the authors designed a knockout model for the fragile X syndrome in mice and found that the knockout mice lack normal Fmr1 protein and show macroorchidism, learning deficits, and hyperactivity.

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981 citations

Journal Article•DOI•

Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development.

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George W. Smith¹, Jean-Michel Aubry¹, Françoise Dellu², Angelo Contarino², Louise M. Bilezikjian¹, Lisa H. Gold², Ruoping Chen¹, Yelena Marchuk¹, Chris Hauser¹, Cornelia A. Bentley¹, Paul E. Sawchenko¹, George F. Koob², Wylie Vale¹, Kuo-Fen Lee¹ - Show less +10 more•Institutions (2)

Salk Institute for Biological Studies¹, Scripps Research Institute²

01 Jun 1998-Neuron

TL;DR: Results suggest that CRFR1 plays an important role both in the development of a functional HPA axis and in mediating behavioral changes associated with anxiety.

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862 citations

Cites background from "Preliminary report of a simple anim..."

...…an increased approach to environments gener- of arginine vasopressin (another key regulator of ACTH secretion) in the PVN of CRFR1-deficient mice was simi-ally considered as aversive in rodents (Denenbergh, 1967; Archer, 1973; Crawley and Goodwin, 1980; Misslin lar to that of control animals....
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Journal Article•DOI•

Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior

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Joseph A. Gogos¹, Maria A. Morgan¹, Victoria N. Luine², Miklós Sántha³, Sonoko Ogawa¹, Donald W. Pfaff¹, Maria Karayiorgou¹ - Show less +3 more•Institutions (3)

Rockefeller University¹, City University of New York², Hungarian Academy of Sciences³

18 Aug 1998-Proceedings of the National Academy of Sciences of the United States of America

TL;DR: The results provide conclusive evidence for an important sex- and region-specific contribution of COMT in the maintenance of steady-state levels of catecholamines in the brain and suggest a role for comT in some aspects of emotional and social behavior in mice.

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Abstract: Catechol-O-methyltransferase (COMT) is one of the major mammalian enzymes involved in the metabolic degradation of catecholamines and is considered a candidate for several psychiatric disorders and symptoms, including the psychopathology associated with the 22q11 microdeletion syndrome. By means of homologous recombination in embryonic stem cells, a strain of mice in which the gene encoding the COMT enzyme has been disrupted was produced. The basal concentrations of brain catecholamines were measured in the striatum, frontal cortex, and hypothalamus of adult male and female mutants. Locomotor activity, anxiety-like behaviors, sensorimotor gating, and aggressive behavior also were analyzed. Mutant mice demonstrated sexually dimorphic and region-specific changes of dopamine levels, notably in the frontal cortex. In addition, homozygous COMT-deficient female (but not male) mice displayed impairment in emotional reactivity in the dark/light exploratory model of anxiety. Furthermore, heterozygous COMT-deficient male mice exhibited increased aggressive behavior. Our results provide conclusive evidence for an important sex- and region-specific contribution of COMT in the maintenance of steady-state levels of catecholamines in the brain and suggest a role for COMT in some aspects of emotional and social behavior in mice.

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855 citations

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References

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Journal Article•DOI•

Benzodiazepine receptor: demonstration in the central nervous system

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Hanns Möhler¹, T Okada¹•Institutions (1)

Hoffmann-La Roche¹

25 Nov 1977-Science

TL;DR: Competition for the receptor by various benzodiazepines closely parallels their pharmacological potency, and binding to the receptor is stereospecific.

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Abstract: Diazepam, a potent minor tranquilizer, binds with high affinity to a specific benzodiazepine receptor that occurs exclusively in the central nervous system. The receptor is mainly localized in the synaptic membrane fraction. Binding to the receptor is stereospecific. Competition for the receptor by various benzodiazepines closely parallels their pharmacological potency.

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1,589 citations

Journal Article•DOI•

Benzodiazepine receptors in rat brain

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Squires Rf, Brastrup C

21 Apr 1977-Nature

TL;DR: Experiments suggest that another important group of psychoactive drugs, the benzodiazepines, bind to specific receptors on the membranes of rat brain cells, and this suggests that there may be an unknown endogenous neurotransmitter which is the natural ligand for the Benzodiazepine receptor.

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Abstract: HIGH affinity binding of tritium labelled morphine and morphine-like drugs to membranes in brain homogenates1–3 was a decisive advance in the characterisation of opiate receptors and the discovery of enkephalines and endorphines We report here experiments which suggest that another important group of psychoactive drugs, the benzodiazepines, bind to specific receptors on the membranes of rat brain cells This suggests that there may be an unknown endogenous neurotransmitter which is the natural ligand for the benzodiazepine receptor The binding sites are distributed unevenly through the brain, and displacement potencies of benzodiazepines correlate with pharmacological effects predictive of anxiolytic activity

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1,399 citations

Journal Article•DOI•

A simple and reliable conflict procedure for testing anti-anxiety agents.

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John R. Vogel, Bernard Beer, Donald E. Clody

01 Jan 1971-Psychopharmacology

TL;DR: The results indicated that this simple procedure clearly demonstrated “anti-anxiety” (i.e., increases in punished responding) effects with benzodiazepines, meprobamate and pentobarbital.

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Abstract: The effects of three benzodiazepines (chlordiazepoxide, diazepam, and oxazepam), meprobamate, pentobarbital, d-amphetamine sulfate, magnesium pemoline, and scopolamine hydrobromide were studied with a simple conflict procedure in which thirsty naive rats were periodically administered shocks for licking water. The results indicated that this simple procedure clearly demonstrated “anti-anxiety” (i.e., increases in punished responding) effects with benzodiazepines, meprobamate and pentobarbital. Doses of d-amphetamine sulfate, magnesium pemoline, and scopolamine hydrobromide did not increase responding.

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809 citations

Journal Article•DOI•

The effects of meprobamate, barbiturates, d-amphetamine and promazine on experimentally induced conflict in the rat

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Irving Geller, Joseph Seifter

01 Nov 1960-Psychopharmacology

TL;DR: The technique permits a separation on a behavioral basis of meprobamate, pentobarbital and phenobarbitals from promazine and d-amphetamine from promazines and d -amphetamine.

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Abstract: Conflict behavior was induced in rats by simultaneously rewarding with liquid food and punishing with pain shock every lever response made in the presence of a tone. Meprobamate, phenobarbital and pentobarbital increased the number of shocks a rat would accept in order to obtain the food reward; in contrast, promazine and d-amphetamine decreased the number of shocks taken. The technique thus permits a separation on a behavioral basis of meprobamate, pentobarbital and phenobarbital from promazine and d-amphetamine.

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751 citations

Book•

Studies in animal and human behaviour

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Konrad Lorenz

01 Jan 1970

577 citations