Amygdaloid GABA, not glutamate neurotransmission or mRNA transcription controls footshock-associated fear arousal in the acoustic startle paradigm

In Pavlovian conditioning the fear-evoking properties of the aversive unconditioned stimulus are represented by the conditioned stimulus. A major challenge for theories of classical fear conditioning has been to understand how associations are formed between a conditioned stimulus and unconditioned stimulus. Although the cellular mechanisms in the amygdala that underlie fear learning have received considerable attention relatively little is known about the neural substrates underlying unconditioned stimulus-associated fear. In the present study we examined the role of GABAA, N-methyl-d-aspartic acid and non-N-methyl-d-aspartic acid receptors, and protein synthesis inhibition on the immediate fear arousal produced by footshock as measured by the shock sensitization of acoustic startle. Laboratory rats showed shock-enhanced startle after infusion into the basolateral amygdala of the N-methyl-d-aspartic acid receptor antagonist d(−)-2-amino-5-phosphonopentanoic acid (5.0μg), the non-N-methyl-d-aspartic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione disodium (5.0μg) and the protein synthesis inhibitor anisomycin (80.0μg). We concluded that fear arousal provoked by footshock is not mediated by glutamate neurotransmission in the amygdala and does not involve de novo protein synthesis. Bilateral infusion into the basolateral amygdala of the GABAA receptor agonist muscimol in doses ranging from 0.001–0.5μg reliably blocked the shock sensitization of acoustic startle responding. None of the muscimol doses altered shock reactivity amplitudes indicating the normal perception of footshock. The muscimol results were interpreted to suggest that decreased GABA neurotransmission in the amygdala may be essential for the neural causation of fear that is acquired and expressed by conditioned stimuli.