Bortz_2013_Neurosci_255_55

The ability of local infusions of the alpha 7 nicotinic acetycholine receptor (alpha7 nAChR) partial agonist SSR180711 to evoke glutamate release in prefrontal cortex was determined in awake rats using a microelectrode array. Infusions of SSR180711 produced dose-dependent increases in glutamate levels. The lower dose (1.0mug in 0.4muL) evoked a rapid rise ( approximately 1.0s) in glutamate (1.41+/-0.30muM above baseline). The higher dose (5.0mug) produced a similarly rapid, yet larger increase (3.51+/-0.36muM above baseline). After each dose, the glutamate signal was cleared to basal levels within 7-18s. SSR180711-evoked glutamate was mediated by the alpha7 nAChR as co-infusion of the selective alpha7 nAChR antagonist alpha-bungarotoxin (10.0muM)+SSR1808711 (5.0mug) reduced the effect of 5.0mug alone by 87% (2.62 vs. 0.35muM). Finally, the clearance of the SSR180711 (5.0mug)-evoked glutamate was bidirectionally affected by drugs that inhibited (threo-beta-benzyl-oxy-aspartate (TbetaOA), 100.0muM) or facilitated (ceftriaxalone, 200mg/kg, i.p.) excitatory amino acid transporters. TbetaOA slowed both the clearance (s) and rate of clearance (muM/s) by 10-fold, particularly at the mid-late stages of the return to baseline. Ceftriaxone reduced the magnitude of the SSR180711-evoked increase by 65%. These results demonstrate that pharmacological stimulation of alpha7 nAChRs within the prefrontal cortex is sufficient to evoke rapid yet transient increases in glutamate levels. Such increases may underlie the cognition-enhancing effects of the drug in animals; further justifying studies on the use of alpha7 nAChR-positive modulators in treating cognition-impairing disorders in humans.