Effects of centrally administered anxiolytic agents on classically conditioned bradycardia.

Rats received infusions of the opioid peptide D-Ala2-Met-enkephalinamide (DALA, 10 micrograms), the alpha 2-noradrenergic agonist clonidine (CLON, 3 micrograms), UK14,304 (UK, 5 micrograms), the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF (9-41) (alpha-HEL, 25 micrograms), or saline in the rostral fourth ventricle. The DALA, CLON, and UK groups showed no evidence of a heart rate (HR) conditioned response (CR) during conditioning, after antagonist administration, or on a nondrug test 48 hr after conditioning. These three groups showed the development of normal CRs when later retrained without drugs. The alpha-HEL group showed an enhanced CR. During a subsequent startle test, the presence of a conditioned stimulus resulted in a pronounced suppression of startle in the SAL and alpha-HEL groups but had no effects on startle in the DALA, CLON, and UK groups. The results indicate an important role for fourth ventricle structures containing opioid and alpha 2 receptors in the learning of an HR CR.