Effects of CNS Norepinephrine Reuptake Inhibitor upon the Arterial Blood Pressure Conditional Response in Rat

Abstract

This study examined the effects of a central NE reuptake transporter inhibitor (tomoxetine, T) upon the arterial BP conditional response (CR). Rats were classically conditioned to two stimuli: a 15 sec. pulsed tone (CS+) followed by a 0.5 sec. tail shock and a 15 sec steady tone (CS-) never followed by shock. CS+ evokes a sudden, transient, increase in arterial BP (C1) followed by a smaller, but sustained pressor response (C2). C1 derives from an orienting response; C2 must be learned as the rat acquires the CR with repeated pairings (AJP 289:R784). CS- evokes a C1, but little or no C2. Rats were trained in both tones over the course of 1 week. Three days of control CR data were obtained (i.e., without drug or saline (S)). Animals were then tested for 3 days after S (n=4) or after T (n=4; 1 mg/kg sc). Preliminary findings indicate that C1 and C2 were unchanged for control vs S. C1 was unchanged vs control after T, but C2 was increased following T (7.4 ± 3.1 mm Hg, mean ± SD) vs. no-drug control (5.2 ± 3.4 mm Hg), suggesting that drug treatment accentuated the “learned” component of the conditional response. CS- after T evoked a larger C2 (5.1 ± 1.9 mm Hg) than control (2.8 ± 1.5 mm Hg), indicating T may interfere with discrimination between CS+ and CS-. These findings suggest that C1 and C2 are mediated by different central processes (cf: AJP 248: H1793). (Supported by NIH grant NS39774)