Heart rate conditioning with pentobarbital as a conditioned stimulus and amphetamine as an unconditioned stimulus.

Pentobarbital was injected into rats 20 min after they were placed in an apparatus where heart rates were recorded. Amphetamine was injected after they were removed from the apparatus 29-30 min later. A Pavlovian conditioned response (CR) began after three or four such trials in the form of a failure of conditioned rats to show the same decline in heart rate obtained in controls after the pentobarbital injection. On later trials, the amphetamine was not injected until 50 min after the pentobarbital, and the CR was most obvious during the period 30-50 min after the pentobarbital injection, an effect characteristic of Pavlovian delay conditioning. The pharmacological effects of pentobarbital were necessary for conditioning because the CR was not obtained (a) when normal saline was substituted for the pentobarbital after successful conditioning or (b) when saline was used instead of pentobarbital throughout. Because of the speed and effectiveness of the conditioning, we believe the mechanism responsible for it has homeostatic regulation as its natural role. It was puzzling that environmental cues seemed to have a role in the conditioned stimulus complex, because conditioning was not apparent when the drug-drug pairings were administered in the home cage.