Behavioral and physiological detection of classically-conditioned blood pressure reduction

Spontaneously hypertensive (SH) rats were trained to discriminate the effects of saline injection from the interoceptive stimuli associated with the blood-pressure-reducing effect of clonidine (0.02 mg/kg, IP) in a drug discrimination procedure. Anise/ethanol and ethanol odors were then systematically paired with clonidine and saline treatment, respectively, outside the drug discrimination setting. As the number of pairings increased, the anise/ethanol (but not the ethanol) stimulus, when given alone, came to both reduce blood pressure and to mimic clonidine's interoceptive stimulus to virtually the same extent as clonidine itself. Both responses induced by the conditioned stimulus (CS+; anise/ethanol odor) were antagonized by the noradrenergic alpha-2 receptor antagonist yohimbine at a dose that did not by itself influence blood pressure. These data support the hypothesis that activation of endogenous factors can be elicited by a CS, and that these factors may furthermore act agonistically at central alpha-2 receptors to reduce blood pressure in hypertensive animals.