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Volume 17, Number 5, Issue of March 1, 1997 pp. 1838-1847
Copyright ©1997 Society for Neuroscience

Activation of Amygdala Cholecystokinin_B Receptors Potentiates the Acoustic Startle Response in the Rat

Received Oct. 16, 1996; revised Dec. 12, 1996; accepted Dec. 16, 1996.

Paul W. Frankland¹, Sheena A. Josselyn¹, Jacques Bradwejn², Franco J. Vaccarino^{1, 2}, and John S. Yeomans¹

¹ Department of Psychology, University of Toronto, Toronto, Ontario, Canada M5S 1A1, and ² Mood and Anxiety Division, Clarke Institute of Psychiatry, Toronto, Ontario, Canada M5T 1R8

The acoustic startle reflex is a sensitive index of "anxiety" and "fear." Potentiation of startle by conditioned and unconditioned fear stimuli appears to be mediated by the amygdala. Cholecystokinin_B (CCK_B) agonists increase "anxiety" in laboratory animals and induce "panic" in humans. Here, we investigate the role CCK_B receptor-mediated mechanisms in the amygdala in the potentiation of startle. First, intra-amygdala infusions of the CCK_B receptor agonist pentagastrin (0, 0.01, 0.1, 1, and 10 nM) produced a dose-related potentiation of acoustic startle responses. At the highest dose, startle amplitudes were increased up to 90% above preinfusion baseline levels. Second, similar infusions of pentagastrin had no effect on locomotor activity over the same time course, showing that increases in startle responsivity after infusions of pentagastrin are not attributable to nonspecific changes in motor activity. Third, infusions of similar doses of pentagastrin into the striatum or nucleus accumbens did not potentiate startle responses. Fourth, pretreatment with the CCK_B receptor antagonist L-365,260 (0.1 mg/kg, i.p.) attenuated the potentiation of startle produced by intra-amygdala infusions of pentagastrin. Finally, intra-amygdala infusion of the CCK_B receptor-selective antagonist PD-135158 (10 µg) blocked the potentiation of startle produced by i.c.v. infusions of pentagastrin, suggesting that i.c.v. infusions of pentagastrin potentiate startle responses via activation of amygdala CCK_B receptors. These results show that amygdala CCK_B receptor-mediated mechanisms are involved in the potentiation of acoustic startle responses.

Key words: startle; anxiety; fear; locomotor activity; i.c.v.; microinjection; pentagastrin; cholecystokinin; striatum; PD-135158; L-365,260

This article has been cited by other articles:

				L. Chung and S. D. Moore Cholecystokinin Excites Interneurons in Rat Basolateral Amygdala J Neurophysiol, July 1, 2009; 102(1): 272 - 284. [Abstract] [Full Text] [PDF]

				S. J. Tavernor, K. A. J. Abduljawad, R. W. Langley, C. M. Bradshaw, and E. Szabadi Effects of pentagastrin and the cold pressor test on the acoustic startle response and pupillary function in man J Psychopharmacol, July 1, 2000; 14(4): 387 - 394. [Abstract] [PDF]

				J. Shlik, Y. Zhou, D. Koszycki, F. J. Vaccarino, and J. Bradwejn Effects of CCK-4 infusion on the acoustic eye-blink startle and psychophysiological measures in healthy volunteers J Psychopharmacol, July 1, 1999; 13(4): 385 - 390. [Abstract] [PDF]

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