Drug-drug heart rate conditioning in rats: effective USs when pentobarbital is the CS

Injections of two drugs in sequence may be considered the Pavlovian pairing of one drug as a conditioned stimulus (CS) with a second drug as an unconditioned stimulus (US). If pentobarbital was the CS and d-amphetamine or nicotine sulfate the US, then after about four drug-drug pairings the pentobarbital CS produced a higher heart rate (HR) than control conditions. With the same pentobarbital CS, HR conditioning was not obtained with the following USs: atropine, caffeine, lithium chloride, continuous foot-shock, and intermittent foot-shock. Although amphetamine and nicotine are pharmacologically different, a common conditioning mechanism seems indicated because of striking similarities in their parametric effects as USs. There also were strong similarities in these two USs when the conditioned response was a reduced capacity of the CS drug to produce conditioned taste aversions.