Recently developed ethoexperimental tests aimed at description and analysis of defensive reactions to the presence of unconditioned, nonpainful threat stimuli, or to situations associated with such stimuli, indicate substantial differences between the two. Present threat stimuli (in the FEAR/DEFENSE TEST BATTERY) elicit reactions such as flight, freezing, and defensive threat and attack, while situations associated with threat (in the ANXIETY/DEFENSE TEST BATTERY) produce a pattern of time-based changes from avoidance/movement inhibition, through risk assessment and interference with nondefensive behaviors. These two patterns, fitting the traditional psychological division between fear and anxiety, provide a full range of defensive behaviors for analysis of bidirectional changes in behavior associated with administration of pharmacological compounds. Since these tests do not use painful stimuli or involve learning of reactions to stimuli associated with pain, they are analytically less complex than traditional anxiety models, while providing a wider range of behavioral measures. Work completed with benzodiazepine and 5-HT1A agonists suggests a close correspondence between effects on these models and the clinical efficacy of pharmacological agents. The proposed program will examine the usefulness of these test batteries, plus a more inclusive VISIBLE BURROW SYSTEM test, as models for investigating the effects of pharmacological compounds previously shown to alter fear or anxiety reactions. These compounds include Benzodiazepine, GABA, 5-HT, Dopamine, Noradrenalin and Colinergic agonists and antagonists, plus Anti- Panic Agents. The effects of these drugs on wild and laboratory rats in these test batteries will provide an extremely detailed behavioral profile form each compound, and will permit in-depth comparisons within and between the different classes of compounds. This data base should thus enable much finer analysis of the effects of pharmacological manipulations on fear/anxiety reactions, resulting in increased understanding of the neurobiology of this system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH042803-02
Application #
3382108
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1989-05-01
Project End
1992-04-30
Budget Start
1990-05-01
Budget End
1991-04-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Hawaii
Department
Type
Organized Research Units
DUNS #
121911077
City
Honolulu
State
HI
Country
United States
Zip Code
96822
Blanchard, D C; Griebel, G; Rodgers, R J et al. (1998) Benzodiazepine and serotonergic modulation of antipredator and conspecific defense. Neurosci Biobehav Rev 22:597-612
Blanchard, R J; Griebel, G; Henrie, J A et al. (1997) Differentiation of anxiolytic and panicolytic drugs by effects on rat and mouse defense test batteries. Neurosci Biobehav Rev 21:783-9
Blanchard, D C; Spencer, R L; Weiss, S M et al. (1995) Visible burrow system as a model of chronic social stress: behavioral and neuroendocrine correlates. Psychoneuroendocrinology 20:117-34
Griebel, G; Blanchard, D C; Jung, A et al. (1995) 5-HT1A agonists modulate mouse antipredator defensive behavior differently from the 5-HT2A antagonist pirenperone. Pharmacol Biochem Behav 51:235-44
Griebel, G; Blanchard, D C; Jung, A et al. (1995) Further evidence that the mouse defense test battery is useful for screening anxiolytic and panicolytic drugs: effects of acute and chronic treatment with alprazolam. Neuropharmacology 34:1625-33
Monder, C; Sakai, R R; Miroff, Y et al. (1994) Reciprocal changes in plasma corticosterone and testosterone in stressed male rats maintained in a visible burrow system: evidence for a mediating role of testicular 11 beta-hydroxysteroid dehydrogenase. Endocrinology 134:1193-8
Blanchard, R J; Yudko, E B; Rodgers, R J et al. (1993) Defense system psychopharmacology: an ethological approach to the pharmacology of fear and anxiety. Behav Brain Res 58:155-65
Blanchard, D C; Sakai, R R; McEwen, B et al. (1993) Subordination stress: behavioral, brain, and neuroendocrine correlates. Behav Brain Res 58:113-21
Blanchard, R J; Magee, L; Veniegas, R et al. (1993) Alcohol and anxiety: ethopharmacological approaches. Prog Neuropsychopharmacol Biol Psychiatry 17:171-82
Blanchard, R J; Taukulis, H K; Rodgers, R J et al. (1993) Yohimbine potentiates active defensive responses to threatening stimuli in Swiss-Webster mice. Pharmacol Biochem Behav 44:673-81

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