SUBSTANCE-P IS INVOLVED IN THE SENSITIZATION OF THE ACOUSTIC STARTLE RESPONSE BY FOOTSHOCKS IN RATS

The acoustic startle response (ASR) can be enhanced by administration of footshocks (sensitization). The neural mechanisms underlying this e ffect are largely unknown. A previous electrophysiological study (Kung el et al., Brain Res., 643 (1994) 29-39) has shown that the neuropepti de substance P (SP) increases the responsiveness to acoustic stimuli o f neurons in the caudal pontine reticular nucleus (PnC). Since the PnC is an important part of the primary acoustic startle circuit, we hypo thesized that SP is involved in the enhancement of the ASR by electric footshocks. We tested this hypothesis in different experiments by loc ally injecting SP and SP-antagonists into the PnC of freely moving rat s. The present data show that SP (0.5 pmol-1 nmol) locally injected in to the PnC dose-dependently increases the amplitude of the ASR in rats . This effect was antagonized by pretreatment with the SP-antagonist C P-96,345. Furthermore, we show that the sensitization of the ASR by 0. 6 mA-footshocks can be blocked by local microinjections of the SP-anta gonists CP-96,345 (5 pmol-10 nmol) or CP-99,994 (0.5 nmol-100 nmol) in to the PnC. Possible pathways relevant for the sensitization of the AS R are discussed.