Figure 1.

Lesion studies demonstrated that stimulation post-synaptic alpha-2 receptors in dlPFC improves working memory function^A: Rhesus monkeys with 6-OHDA lesions or ablations of the dlPFC (red area) were treated with the alpha-2 agonist, clonidine, prior to performing a spatial working memory task. Clonidine’s potency related to the degree of NE depletion from dlPFC, consistent with actions at post-synaptic alpha-2 receptors in this region (Adapted from Arnsten & Goldman-Rakic, 1985); B: Rhesus monkeys were treated with chronic reserpine to deplete monoamines globally, a classic test for pre- v.s. post-synaptic drug actions. Clonidine’s beneficial effects on spatial working memory were enhanced following reserpine treatment, consistent with a post-synaptic site of drug action (Adapted from Cai et al, 1993).