The role of GABA and anxiety in the reconsolidation of conditioned fear.
The current study examined the effects of systemic administration of a GABA agonist [midazolam (MDZ)] and a GABA antagonist (bicuculline) on fear responding after brief CS exposure, a procedure thought to involve memory reconsolidation. Using a contextual fear-conditioning paradigm, rats were initially given two context-shock training trials, followed 24 hrs later by a 90-s context exposure (reactivation), and 24 hrs later by a 3-min context test. In Experiment 1, MDZ (2 mg/kg, i.p.), whereas in Experiment 2, bicuculline (1 mg/kg, i.p.), was administered immediately after reactivation. MDZ reduced conditioned freezing, whereas bicuculline only marginally potentiated conditioned freezing. The MDZ fear disruption effect did not occur in the absence of reactivation, and was evident 10 days after the initial test. Experiment 3 induced high levels of baseline anxiety using the single prolonged stress paradigm, and replicated the essential procedure of Experiment 1. Results indicated that MDZ fear disruption did not differ between high and low anxiety rats. The data suggest the involvement of GABA receptors in reconsolidation processes, and the possible clinical use of MDZ in fear reduction with brief reexposure.
Zhang
Shirley
S
School of Psychology, University of New South Wales, Sydney, NSW, Australia.
Cranney
Jacquelyn
J
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D005239:Fear; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008874:Midazolam / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D018757:GABA Modulators; D005680:gamma-Aminobutyric Acid; D008874:Midazolam; D001640:Bicuculline