NMDA receptors in the pontine brainstem are necessary for fear potentiation of the startle response.
The fear-potentiated startle model in rats is a valuable animal test for the investigation of the neural and neurochemical basis of fear. In this model, rats are trained to associate a neutral stimulus with an aversive stimulus, so that after conditioning the conditioned stimulus alone elicits a state of fear leading to an exaggerated acoustic startle response. The fear-potentiated startle model does not require instrumental responding for the indication of states of fear. The acoustic startle response is mediated by a simple brainstem circuit, with the caudal pontine reticular nucleus as an interface that receives input from startle-enhancing circuits. In the present study, we tested the hypothesis that N-methyl-D-aspartate (NMDA) receptors on neurones of the caudal pontine reticular nucleus are involved in the mediation of fear-potentiated startle. After fear-conditioning, we injected the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP-5), into the caudal pontine reticular nucleus of awake rats and tested the effect on the expression of fear-potentiated startle. Injections of AP-5 (0.125-0.5 nmol) into the caudal pontine reticular nucleus dose dependently attenuated fear-potentiated startle without affecting the baseline amplitude of the acoustic startle response. The results suggests that, in the caudal pontine reticular nucleus, glutamate may mediate fear-potentiated startle via NMDA receptors.
Fendt
M
M
Universität Tübingen, Germany.
Koch
M
M
Schnitzler
H U
HU
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000161:Acoustic Stimulation; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear / Q000502:physiology*; D008297:Male; D011149:Pons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013216:Reflex, Startle / Q000502:physiology*; D012154:Reticular Formation / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate