title: Evidence that long-lasting potentiation of amygdala efferents in the right hemisphere underlies pharmacological stressor (FG-7142) induced lasting increases in anxiety-like behaviour: role of GABA tone in initiation of brain and behavioural changes.
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.
authors.affiliation: Department of Psychology, Memorial University, St Johns, NF.
authors.forename: R E
authors.initials: RE
authors.lastname: Adamec
mesh_terms: D000374:Aggression / Q000187:drug effects*; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced* / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology; D002415:Cats; D004525:Efferent Pathways / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology; D007839:Functional Laterality / Q000502:physiology*; D018755:GABA Agonists / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D007033:Hypothalamus, Middle / Q000502:physiology; D008297:Male; D011235:Predatory Behavior / Q000187:drug effects; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects; D013315:Stress, Psychological / Q000139:chemically induced* / Q000523:psychology*; D020888:Vigabatrin / Q000494:pharmacology; D014828:Vocalization, Animal / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000927:Anticonvulsants; D002243:Carbolines; D018755:GABA Agonists; D018757:GABA Modulators; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C035874:FG 7142; D020888:Vigabatrin