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ANESTHETIC PHARMACOLOGY

Short-Term Memory Resists the Depressant Effect of the Nonimmobilizer 1-2-Dichlorohexafluorocyclobutane (2N) More than Long-Term Memory

Robert C. Dutton, MD^*, Anya J. Maurer, BS^*, James M. Sonner, MD^*, Michael S. Fanselow, PhD, Michael J. Laster, DVM^*, and Edmond I Eger, II, MD^*

*Department of Anesthesia and Perioperative Care, University of California, San Francisco; and Department of Psychology, University of California, Los Angeles, California

Address correspondence to Dr. Robert C. Dutton, Department of Anesthesia, S-455, University of California, San Francisco, CA 94143-0464. Address e-mail to duttonr{at}anesthesia.ucsf.edu

The nonimmobilizer 1,2-dichlorohexafluorocyclobutane (2N, also termed F6) does not suppress movement to noxious stimuli but does suppress learning of fear-potentiated startle. The mechanism whereby 2N suppresses this learning is unknown. Herein, we report the effect of 2N on suppression of two other forms of learning, fear conditioning to context and to tone. Because 2N does not cause sedation, we could study the effect of 2N on short-term memory (memory for fear conditioning measured during or immediately after training) as well as on long-term memory (measured 24 h after training). The EC₅₀ for suppression of long-term memory (the concentration decreasing memory by 50%) of fear conditioning to context was 2.00% ± 0.01% (mean ± SEM), and for fear conditioning to tone was 3.45% ± 0.26%, (P < 0.05). The EC₅₀ for suppression of short-term memory of fear conditioning to context was 2.59% ± 0.21% (P < 0.05, compared with long-term memory of context conditioning), whereas short-term memory of fear conditioning to tone was not suppressed by 3.5%, the largest concentration studied. Thus, short-term memory resists the depressant effect of 2N more than long-term memory, fear conditioning to tone is less vulnerable to the effect of 2N than fear conditioning to context, and 3.5% 2N does not preclude transmission of tone and shock signals to the site where tone-shock associations are formed.

IMPLICATIONS: The nonimmobilizer 1,2-dichlorohexafluorocyclobutane has a greater depressant effect on long-term memory than short-term memory, suggesting that it impairs the processes responsible for the retention of memory more than for the formation of memory itself.