Citation

Adamec RE. J. Psychopharmacol. 2000; 14(4): 323-339.

Copyright

(Copyright © 2000, SAGE Publishing)

DOI

10.1177/026988110001400418

PMID

11198049

Abstract

The hypothesis that long-lasting potentiation (LLP) in amygdala efferents to the periacqueductal gray (PAG) of the right hemisphere mediates initiation of lasting increases in defensive response to rats induced by FG-7142 was supported in this study. GABA transmission was potentiated with Vigabatrin (gamma vinyl GABA, GVG), a suicide inhibitor of GABA transaminase. It was predicted that increasing GABA transmission would interfere with LLP and behavioural changes. The hypothesis was confirmed, for the most part. GVG given 1 day prior to FG-7142 prevented increased defensive response to rats as well as LLP in right amygdala efferent transmission to the PAG. It did not prevent LLP in the left amygdalo-PAG pathway, although LLP duration was shortened. Nor did it prevent LLP in the right amygdalo-ventromedial hypothalamic (VMH) pathway, and LLP in this pathway was associated with a slightly increased response to vocal threat, but not to rats. GVG given without FG-7142 had no behavioural effects, although it did potentiate transmission in the left amygdalo-PAG pathway. The effects of increasing GABA transmission are consistent with the hypothesis that FG-7142 changes behaviour by inducing a failure of GABA transmission, which in turn facilitates NMDA transmission and NMDA dependent limbic LLP. Finally, the hypothesis that altering GABA tone would change the efficacy of Flumazenil from a neutral antagonist to an inverse agonist was tested on limbic transmission. The hypothesis was confirmed in the left amygdalo-VMH pathway, but no other. It was concluded that mechanisms other than a change in GABA tone account for the drug-dependent reversal of LLP in the right amygdalo-PAG by Flumazenil. The findings of the present study suggest that response to FG-7142 may be a useful model of the effects of traumatic stressors on limbic system function in anxiety.

Language: en

Keywords

Aggression; Amygdala; Animals; Anticonvulsants; Anxiety; Behavior, Animal; Brain Chemistry; Carbolines; Cats; Efferent Pathways; Flumazenil; Functional Laterality; GABA Agonists; GABA Modulators; gamma-Aminobutyric Acid; Hypothalamus, Middle; Male; Predatory Behavior; Rats; Receptors, GABA-A; Stress, Psychological; Vigabatrin; Vocalization, Animal