Attention-enhancing effects of propranolol and synergistic effects with nicotine.

Nicotine increases the output of every major neurotransmitter. In previous studies designed to identify the secondary neurotransmitter systems mediating nicotine's attention-enhancing effects in a rat model, the β-adrenoceptor antagonist propranolol blocked these effects. The present study was designed to test whether this mechanism held true in humans, thus guiding development of novel nicotinic agonists for cognitive enhancement. Twenty-six nonsmokers completed a nicotine (7 mg/24 h transdermally) x propranolol (40 mg p.o., body weight-adjusted) interaction study. Over four test days, each participant received double-placebo, nicotine only, propranolol only, and nicotine plus propranolol in randomized sequence before cognitive testing. No drug effects were seen in a visuospatial attention task. In the Rapid Visual Information Processing Task, performed in two 15-min blocks, neither drug alone significantly affected hit rate, but both drugs combined acted synergistically to alleviate its decrement over time in the first block and displayed additive beneficial effects in the second. In a change detection task, propranolol enhanced accuracy and reduced reaction time independent of nicotine presence. Propranolol also enhanced subjective self-reports of vigor. Overall, the findings were contrary to those hypothesized. Propranolol displayed beneficial effects on cognition, especially on sustaining performance over time. β-adrenoceptor activation by nicotine-induced noradrenaline release appeared to limit performance-enhancing effects of nicotine, because they were unmasked by β-adrenoceptor antagonism. The results suggest that cognitive effects of changes in β-adrenoceptor tone are context-dependent; contrary to rodent paradigms, human cognitive paradigms require no physical orienting in space but prolonged periods of remaining stationary while sustaining predictable processing demands.