Behavioral Neuroscience 1988, Vol. 102, No. 2, 233-243 Copyright 1988 by the Americ i Psychological Association, Inc. 07 35-7044/88/$00.75 Conditional Analgesia, Defensive Freezing, and Benzodiazepines Michael S. Fanselow and Fred J. Helmstetter Dartmouth College When rats are placed in a situation that has come to be associated with footshock through the process of Pavlovian conditioning, they react with the species-specific defensive response of freezing and a reduction in sensitivity to painful stimulation. In the present experiments, the effects of three benzodiazepines on both of these responses were examined. Pain sensitivity was measured with the formalin test. Concurrent observations of formalin-induced recuperative behavior and freezing were recorded while the animals were in the presence of shock-associated contextual stimuli. It was found that midazolam (Experiments 1 and 2), chlordiazepoxide (Experiment 3), and diazepam (Experiment 4) were capable of significantly attenuating the conditional analgesia. Midazolam and diazepam also reduced the freezing response. The finding that these anxiolytic agents attenuate both conditional responses suggests that the freezing and analgesia are mediated by a common fearlikc process. When a behaviorally impotent stimulus becomes associated with a nociceptive stimulus, such as electric shock, it acquires the ability to provoke several changes in behavior. Conditional stimuli (CS) that have been involved in such a Pavlovian conditioning procedure have been shown to provoke, among other responses, heart rate changes (e.g., Black & de Toledo, 1972; Obrist, Sutterer, & Howard, 1972), suppression of on- going appetitive behavior (e.g., Annau & Kamin, 1961; Bou- ton & Bolles, 1980; Estes & Skinner, 1941), enhancement of avoidance behavior (e.g., Rescorla & LoLordo, 1965), and the species-specific defensive response of freezing (e.g., Bolles & Collier, 1976; Sigmundi, Bouton, & Bolles, 1980). Because of this wide variety of responses to the CS, several theorists have suggested that the CS activates some mediational process such as a central motivational state (e.g., Rescorla & Solomon, 1967). One response to such a CS, which has recently attracted considerable attention, is the CS's ability to reduce sensitivity/ reactivity to painful stimuli (e.g., Chance, Krynock, & Rosc- crans, 1978; Fanselow, 1984; Fanselow & Bolles, 1979; MacLennan, Jackson, & Maier, 1980; Ross & Randich, 1985; Watkins, Cobelli, & Mayer, 1982). This analgesic response is of particular interest to learning theorists because the analgesia produced by the CS might alter the impact of a nociceptive unconditional stimulus (US) and thereby regulate the condi- tioning process itself (Fanselow, 1981, 1986b). Theoretical accounts of conditional analgesia have typically emphasized the role of some mediational process. Chance (1980) suggested that an emotional state, fear, mediates the analgesia produced by the conditioning procedure. Another mediational account suggested by Fanselow (Bolles & Fanse- low, 1980; Fanselow & Sigmundi, 1986) proposed that acti- vation of a defensive motivational system modulates pain sensitivity as well as other overt defensive responses. In gen- This research was supported by National Science Foundation Grant No. 86-06787. All drugs were generously donated by Hoffman- LaRoche Inc., Nutley, New Jersey. Correspondence concerning this article should be addressed to Michael S. Fanselow, Department of Psychology, Dartmouth College, Hanover, New Hampshire 03755. eral, these mediational views hold that a common process is responsible for both the analgesic response and other condi- tional behaviors. 1 The purpose of the present report is to explore the appropriateness of the view that a common me- diational process underlies both analgesic and defensive be- havioral responses conditioned by aversive Pavlovian proce- dures. One line of testing the mediational view is provided by experiments in which stimuli, other than aversive Pavlovian CSs, that should activate the same mediational process are examined. If such stimuli all provoke analgesia, it suggests that a common process mediates the analgesic reaction to these different stimuli. In support of this idea, it has been shown that several "naturalistic" stimuli produce defensive freezing and analgesic responses that are qualitatively similar to those that occur in response to a CS that has undergone aversive Pavlovian conditioning (Fanselow, 1985; Fanselow & Sigmundi, 1986; Lester & Fanselow, 1985). A second line of testing comes from findings that some brain lesions that produce hyperemotionality or heightened defensiveness are accompanied by analgesia (Chance et al., 1978) whereas cer- tain other brain lesions that block overt fear responses also block conditional analgesia (Kinscheck, Watkins, & Mayer, 1984). The present experiments provide another general test of this mediational view by the use of a pharmacological manip- ulation. Because of the anxiolytic properties of benzodiaze- pines, as assessed by various measures with a number of different species (Berg & Davis, 1984; Cook & Sepinwall, 1975; Dantzer, 1977; Treit, Pinel, & Fibiger, 1981), benzodi- 1 There are several different theoretical conceptualizations of this mediational process. These have included helplessness (e.g., Maier, 1986), submissiveness (Miczek, Thompson, & Shuster, 1986), emo- tionality (Chance, 1980), and activation of a defensive motivational system (Fanselow, 1986b). In the present experiments, we do not distinguish between these various theoretical accounts but rather attempt to assess the viability of a mediational account in general. In the present context, we use the term fear more as a convenient label than to imply any particular theoretical alternative. 233 This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.