Comparison of buspirone with diazepam and fluvoxamine on aversive classical conditioning in humans (original) (raw)

1999, Journal of Psychopharmacology

The e¡ects of buspirone, £uvoxamine and diazepam were investigated, using healthy volunteers, in an aversive conditioning paradigm, a putative model for conditioned anxiety. The main prediction was that buspirone, an anxiolytic agent which reduces activity in serotonin (5-hydroxytryptophan, 5-HT) neurones, would attenuate aversively conditioned skin conductance responses. Skin conductance responses were recorded to 10 neutral tones (habituation phase). Tone 11 was immediately followed by a 1-s 90-dB aversive white noise (unconditioned stimulus).The conditioning trial reinstated responding to a second presentation of the tones (extinction phase). Skin conductance response amplitude, inter-response level and spontaneous £uctuations were recorded. There were ¢ve treatment groups comprising ¢ve men and ¢ve women. One control group took placebo, another control group received nothing; there was no e¡ect of placebo on any measure. Diazepam (2 mg, p.o.), a positive comparator, markedly reduced the amplitude of skin conductance responses at all phases of the experiment, but only in women. Buspirone (5 mg, p.o.) had the predicted e¡ect of accelerating extinction but also of unexpectedly accelerated habituation of skin conductance responses. There was a trend to reduce spontaneous £uctuations and no e¡ect on skin conductance level. The e¡ects of buspirone were thus speci¢c to responses to stimuli. Fluvoxamine (25 mg, p.o.) had similar e¡ects to buspirone and diazepam in women. An action common to buspirone, £uvoxamine and diazepam, which may account for their shared e¡ect on conditioned autonomic responses, is the suppression of neural activity in the dorsal raphe nucleus. It is argued that enhanced habituation must involve a di¡erent mechanism, such as enhanced 5-HT 1A function in the terminal ¢elds of the median raphe nucleus.