کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6274260 | 1614821 | 2013 | 13 صفحه PDF | دانلود رایگان |

- SSR180711 led to dose-dependent increases in prefrontal glutamate levels.
- SSR180711-stimulated glutamate release via α7 nicotinic receptors.
- The signal responded to drugs that facilitate or inhibit glutamate transporters.
The ability of local infusions of the alpha 7 nicotinic acetycholine receptor (α7 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 (1.0 μg in 0.4 μL) evoked a rapid rise (â¼1.0 s) in glutamate (1.41 ± 0.30 μM above baseline). The higher dose (5.0 μg) produced a similarly rapid, yet larger increase (3.51 ± 0.36 μM above baseline). After each dose, the glutamate signal was cleared to basal levels within 7-18 s. SSR180711-evoked glutamate was mediated by the α7 nAChR as co-infusion of the selective α7 nAChR antagonist α-bungarotoxin (10.0 μM) + SSR1808711 (5.0 μg) reduced the effect of 5.0 μg alone by 87% (2.62 vs. 0.35 μM). Finally, the clearance of the SSR180711 (5.0 μg)-evoked glutamate was bidirectionally affected by drugs that inhibited (threo-beta-benzyl-oxy-aspartate (TβOA), 100.0 μM) or facilitated (ceftriaxalone, 200 mg/kg, i.p.) excitatory amino acid transporters. TβOA slowed both the clearance (s) and rate of clearance (μM/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 α7 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 α7 nAChR-positive modulators in treating cognition-impairing disorders in humans.
Journal: Neuroscience - Volume 255, 26 December 2013, Pages 55-67