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Volume 17, Number 15, Issue of August 1, 1997 pp. 5928-5935
Copyright ©1997 Society for Neuroscience

AMPA Receptor Facilitation Accelerates Fear Learning without Altering the Level of Conditioned Fear Acquired

Received April 4, 1997; revised May 14, 1997; accepted May 22, 1997.

Michael T. Rogan, Ursula V. Stäubli, and Joseph E. LeDoux

Center for Neural Science, New York University, New York, New York 10003

Rats treated with the AMPA receptor-facilitating drug 1-(quinoxolin-6-ylcarbonyl)piperidine (BDP-12) during training acquired fear conditioning to a tone faster than vehicle-treated controls. The effect on acquisition was dependent on the dose given. BDP-12-treated rats and vehicle-treated controls reached the same level of conditioned fear and extinguished at the same rate. The dissociation of learning rate from these other normally covariant measures suggests that the drug had a specific and isolated effect on acquisition. Controls for drug effects on stimulus sensitivity, locomotor activity, generalized fearfulness, and other performance factors support this interpretation. The known action of BDP-12 on receptor dynamics suggests that its effect on acquisition may be attributed to specific modulation of an AMPA and NMDA receptor-dependent plasticity mechanism. The finding that the drug accelerates acquisition but does not affect the level of conditioned fear acquired parallels the effect of the drug on long-term potentiation (LTP) (increasing the rate but not the ceiling of potentiation) and suggests that common mechanisms may underlie fear conditioning and LTP.

Key words: glutamate; AMPA receptors; NMDA receptors; learning; fear; amygdala

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