Lower brainstem catecholamine afferents to the rat dorsal raphe nucleus

Abstract

A large body of data suggests that the activation of alpha 1 receptors by a tonic noradrenergic input might be responsible for the tonic discharge of the serotonergic neurons of the dorsal raphe nucleus (DRN). To test this hypothesis, it was necessary to determine the origin of the noradrenergic and adrenergic innervation of these neurons. For this purpose, we combined small iontophoretic injections of the sensitive retrograde tracer cholera toxin b subunit (CTb) in the different subdivisions of the DRN with tyrosine hydroxylase immunohistochemistry. After CTb injections in the ventral or dorsal parts of the central DRN, a small number of double-labeled cells was observed in the locus coeruleus (A6 noradrenergic cell group), the A5 noradrenergic group, the dorsomedial medulla (C3 adrenergic cell group), and the lateral paragigantocellular nucleus (C1 adrenergic cell group). After CTb injections in the lateral wings or the dorsal part of the rostral DRN, a similar number of double-labeled cells was seen in C3. Slightly more double-labeled cells were seen in A6 and A5. In addition, a substantial to large number of double-labeled cells appeared in C1, the commissural part of the nucleus of the solitary tract (A2 noradrenergic cell group) and the caudoventrolateral medulla (A1 noradrenergic cell group). These results indicate that the noradrenergic and adrenergic inputs to the DRN arise from all the catecholaminergic cell groups of the lower brainstem except the A7 noradrenergic group. They further reveal the existence of a topographical organization of these afferents to the different subdivisions of the DRN.

Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function

“…Another structure known to modulate the activity of DR neurons is the locus coeruleus (LC), which exerts a stimulatory effect on serotonergic neurons (34). In addition, we recently demonstrated that the function of noradrenergic neurons in the LC can be modulated by NK1R antagonists (35).…”

Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray

“…In fact, the 5-HT neurons receive a fairly dense noradrenergic innervation that exerts a tonic excitation via α 1 -adrenoreceptors (160). However, the contribution of this innervation from LC seems to be minor (143,(161)(162)(163)(164), and more caudally located catecholamine groups may be more important (164). Our results, based on double/triple labeling, are in agreement with this view, showing that the vast majority of galanin nerve terminals lack DBH at the levels analyzed in any case.…”

Effects of disulfiram and dopamine beta-hydroxylase knockout on cocaine-induced seizures

“…Since cocaine is known to inhibit 5-HT transporters (SERT), increases in 5-HT following cocaine administration can lead to accumulation of serotonin in synapses, which in turn can increase seizure activity via 5-HT 2 receptor activation. The serotonergic raphe nuclei receive dense innervation from brainstem noradrenergic nuclei (Baraban and Aghajanian, 1981;Marcinkiewicz et al, 1989;Fritschy and Grzanna, 1990;Peyron et al, 1996), and activation of α 1 -adrenergic receptors increases tonic excitatory activity in the dorsal raphe nucleus (Baraban and Aghajanian, 1980;Vandermaelen and Aghajanian, 1983;Hertel et al, 1998;Pudovkina et al, 2003;Judge and Gartside, 2006). Therefore, Dbh -/-mice should have lower levels of extracellular 5-HT, because they lack the noradrenergic excitatory drive on the serotonergic system.…”