Strychnine: brainstem and spinal mediation of excitatory effects on acoustic startle

Abstract

The present study investigated the effects of the glycine antagonist strychnine on the acoustic startle response in rats. Strychnine (0.25, 0.50, 1.0, 1.25, 1.5 and 2.0 mg/kg) administered intraperitoneally (i.p.) was found to produce a dose-dependent increase in startle amplitude that reached its greatest magnitude within 10-15 min after injection. These doses did not produce convulsions or behavioral activation. In order to localize the site of action of this excitatory strychnine effect, rats were implanted with catheters in the lumbar region of the spinal cord (intrathecal implantation), in the cisterna magna, or in the lateral ventricle and later tested for startle after microinjections of strychnine. Dose-dependent excitatory effects on acoustic startle were found when strychnine was injected onto the spinal cord (3.12-12.5 microgram) or into the cisterna magna (6.25-25.0 microgram), whereas infusion into the lateral ventricle produced inhibition (6.25-25.0 microgram). The peak increases in startle following intrathecal (164%) and intracisternal (144%) strychnine were similar to the increase seen following systemic strychnine (160%). Thus, the excitatory effect of systemic strychnine appears to be mediated in the spinal cord and/or brainstem, consistent with data showing that glycine receptors are primarily localized in the caudal regions of the central nervous system. Furthermore, these results suggest that glycine exerts a tonic inhibitory influence on acoustic startle. The possible relation of such a system to phenomena that involve reduction in startle amplitude (e.g., habituation, pre-pulse inhibition) is discussed.