A 5-HYDROXYTRYPTAMINE(2) AGONIST AUGMENTS GAMMA-AMINOBUTYRIC-ACID AND EXCITATORY AMINO-ACID INPUTS TO NORADRENERGIC LOCUS-CERULEUS NEURONS
A 5-HYDROXYTRYPTAMINE(2) AGONIST AUGMENTS GAMMA-AMINOBUTYRIC-ACID AND EXCITATORY AMINO-ACID INPUTS TO NORADRENERGIC LOCUS-CERULEUS NEURONS
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DOI：
10.1016/0306-4522(93)90262-e
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发表时间：
1993-05-01
期刊：
影响因子：
3.3
通讯作者：
ASTONJONES, G
中科院分区：
文献类型：
--
作者：
CHIANG, C;ASTONJONES, G
We examined the effects of the 5-hydroxytryptamine2 receptor agonist, (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, on spontaneous and evoked discharge of locus coeruleus neurons in the rat. Extracellular recordings were obtained from single locus coeruleus neurons while (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane was injected systemically or locally into the locus coeruleus. Systemic, but not local, administration of (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane decreased spontaneous discharge of locus coeruleus neurons in a dose-dependent manner while simultaneously increasing responses evoked by somatosensory stimulation, consistent with previous studies using 5-hydroxytryptamine2 agonists. Increased responsiveness was observed after both low- and high-intensity stimulation and, in the latter, resulted from the addition of a second, longer latency response after (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane administration, when cells typically responded to each stimulation with two driven spikes instead of one. Both of these effects could be completely reversed by systemic administration of the 5-hydroxytryptamine2 receptor antagonist, ketanserin.Furthemore, we report that: (i) the (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced decrease in spontaneous firing was blocked by local infusion of the GABA antagonists bicuculline or picrotoxin into the locus coeruleus, but not by local infusion of the alpha-2 adrenoceptor antagonist, idazoxan; and (ii) the enhancement of locus coeruleus sensory responses after high-intensity stimulation was blocked by local application of the selective antagonist of N-methyl-D-aspartate receptors, 2-amino-5-phosphonopentanoic acid, but not by local infusion of the preferential antagonist of non-N-methyl-D-aspartate receptors, 6-cyano-7-nitroquinoxaline-2,3-dione. Together, these results lead us to propose that systemic 5-hydroxytryptamine2 agonists influence locus coeruleus indirectly, causing tonic activation of a GABAergic input to the locus coeruleus, and facilitating sensory inputs that act via excitatory amino acid receptors within locus coeruleus.
