ACTIVATION OF AMYGDALA CHOLECYSTOKININ(B) RECEPTORS POTENTIATES THE ACOUSTIC STARTLE RESPONSE IN THE RAT

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) (CC KB) agonists increase ''anxiety'' in laboratory animals and induce ''p anic'' in humans. Here, we investigate the role CCKB receptor-mediated mechanisms in the amygdala in the potentiation of startle. First, int ra-amygdala infusions of the CCKB receptor agonist pentagastrin (0, 0. 01, 0.1, 1, and 10 nM) produced a dose-related potentiation of acousti c startle responses. At the highest dose, startle amplitudes were incr eased up to 90% above preinfusion baseline levels. Second, similar inf usions of pentagastrin had no effect on locomotor activity over the sa me time course, showing that increases in startle responsivity after i nfusions of pentagastrin are not attributable to nonspecific changes i n motor activity. Third, infusions of similar doses of pentagastrin in to the striatum or nucleus accumbens did not potentiate startle respon ses. Fourth, pretreatment with the CCKB receptor antagonist L-365,260 (0.1 mg/kg, i.p.) attenuated the potentiation of startle produced by i ntra-amygdala infusions of pentagastrin. Finally, intra-amygdala infus ion of the CCKB receptor-selective antagonist PD-135158 (10 mu g) bloc ked the potentiation of startle produced by i.c.v. infusions of pentag astrin, suggesting that i.c.v. infusions of pentagastrin potentiate st artle responses via activation of amygdala CCKB receptors. These resul ts show that amygdala CCKB receptor-mediated mechanisms are involved i n the potentiation of acoustic startle responses.