Pharmacological separation of mechanisms contributing to human contrast sensitivity

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Two basic types of cholinergic receptor have been identified in nervous systems: nicotinic and muscarinic. In the mammalian visual system, the balance of evidence suggests that nicotinic activity is associated primarily with transmission and processing of information while muscarinic activity reflects modulatory influences arising in the brainstem and basal forebrain. We have measured contrast sensitivity functions using a two-alternative forced-choice procedure in young human volunteers with and without administration of nicotine (1.5 mg by buccal absorption) or the muscarinic antagonist scopolamine (1.2 mg orally). Scopolamine elevates contrast-detection thresholds uniformly at all spatial frequencies, consistent with blocking of a nonspecific arousal system. Nicotine, in contrast, improves sensitivity at low spatial frequencies (below about 4 cycle/deg); at higher spatial frequencies sensitivity is, if anything, impaired. Using counterphase gratings, we find that scopolamine elevates thresholds uniformly at all temporal frequencies. Nicotine lowers thresholds at high but not low temporal frequencies. The results obtained with nicotine suggest that contrast sensitivity reflects the activity of two mechanisms, or sets of spatiotemporal filters, that are pharmacologically distinct, the contrast sensitivity function reflecting the envelope of their sensitivities.