Alpha-2 adrenergic modulation of prefrontal cortical neuronal activity related to spatial working memory in monkeys

The effects of systemically administered or iontophoretically applied clonidine (alpha-2 adrenergic agonist) and iontophoretically applied yohimbine (alpha-2 adrenergic antagonist) were examined on prefrontal cortical (PFC) neurons related to spatial working memory (SWM). Systemically administered clonidine (0.04 mg/kg) enhanced SWM-related PFC neuronal activity by 32.5 +/- 14.5%, (mean +/- SD; n = 25 neurons). The facilitatory effect of clonidine was antagonized by iontophoretically applied yohimbine. Iontophoretically applied clonidine enhanced SWM-related PFC neuronal activity by 38.2 +/- 18.6%, (n = 13 neurons), whereas similarly applied yohimbine suppressed it by 34.4 +/- 17.8% (n = 28 neurons). These results indicate that: a) systemically administered clonidine can facilitate SWM-related PFC neuronal activity through actions at alpha-2 adrenoceptors In the PFC; and b) conversely, blockade by yohimbine of alpha-2 adrenoceptors in the PFC suppresses SWM-related neuronal activity. The present study provides neurophysiological evidence that alpha-2 adrenoceptors in the PFC are involved in the cellular mechanisms underlying working memory. [Neuropsychopharmacology 21:601-610, 1999] (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.