C. Chiang et G. Astonjones, A 5-HYDROXYTRYPTAMINE(2) AGONIST AUGMENTS GAMMA-AMINOBUTYRIC-ACID ANDEXCITATORY AMINO-ACID INPUTS TO NORADRENERGIC LOCUS-CERULEUS NEURONS, Neuroscience, 54(2), 1993, pp. 409-420
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 systemica
lly or locally into the locus coeruleus. Systemic, but not local, admi
nistration of (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane decre
ased spontaneous discharge of locus coeruleus neurons in a dose-depend
ent manner while simultaneously increasing responses evoked by somatos
ensory stimulation, consistent with previous studies using 5-hydroxytr
yptamine2 agonists. Increased responsiveness was observed after both l
ow- and high-intensity stimulation and, in the latter, resulted from t
he addition of a second, longer latency response after (+/-)1-(2,5-dim
ethoxy-4-iodophenyl)-2-aminopropane administration, when cells typical
ly responded to each stimulation with two driven spikes instead of one
. Both of these effects could be completely reversed by systemic admin
istration of the 5-hydroxytryptamine2 receptor antagonist, ketanserin.
Furthemore, we report that: (i) the 2,5-dimethoxy-4-iodophenyl)-2-ami
nopropane-induced decrease in spontaneous firing was blocked by local
infusion of the GABA antagonists bicuculline or picrotoxin into the lo
cus coeruleus, but not by local infusion of the alpha-2 adrenoceptor a
ntagonist, idazoxan; and (ii) the enhancement of locus coeruleus senso
ry responses after high-intensity stimulation was blocked by local app
lication 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 prop
ose that systemic 5-hydroxytryptamine2 agonists influence locus coerul
eus indirectly, causing tonic activation of a GABAergic input to the l
ocus coeruleus, and facilitating sensory inputs that act via excitator
y amino acid receptors within locus coeruleus.