Possible dopaminergic stimulation of locus coeruleus α1‐adrenoceptors involved in behavioral activation

Abstract

α1-Adrenoceptors of the locus coeruleus (LC) have been implicated in behavioral activation in novel surroundings, but the endogenous agonist that activates these receptors has not been established. In addition to the canonical activation of α1-receptors by norepinephrine (NE), there is evidence that dopamine (DA) may also activate certain brain α1-receptors. This study examined the contribution of DA to exploratory activity in a novel cage by determining the effect of infusion of various dopaminergic and adrenergic drugs into the mouse LC. It was found that the D2/D3 agonist, quinpirole, which selectively blocks the release of CNS DA, produced a dose-dependent and virtually complete abolition of exploration and all movement in the novel cage test. The quinpirole-induced inactivity was significantly attenuated by coinfusion of DA but not by the D1 agonist, SKF38390. Furthermore, the DA attenuation of quinpirole inactivity was blocked by coinfusion of the α1-adrenergic receptor antagonist, terazosin, but not by the D1 receptor antagonist, SCH23390. LC infusions of either quinpirole or terazosin also produced profound inactivity in DA-β-hydroxylase knockout (Dbh −/−) mice that lack NE, indicating that their behavioral effects were not due to an alteration of the release or action of LC NE. Measurement of endogenous DA, NE, and 5HT and their metabolites in the LC during exposure to the novel cage indicated an increase in the turnover of DA and NE but not 5HT. These results indicate that DA is a candidate as an endogenous agonist for behaviorally activating LC α1-receptors and may play a role in the activation of this nucleus by novel surroundings.

Locus coeruleus and dorsal raphe neuron activity and response to acute antidepressant administration in a rat model of Parkinson's disease

“…However, no effects have been found with the dopaminergic agonists quinpirole, pramipexole or apomorphine (Cedarbaum & Aghajanian, 1977 ;Chernoloz et al 2009 ;Guiard et al 2008b). On the other hand, dopamine may also stimulate the LC acting on a 1 -adrenoceptors (Lin et al 2008). In our study, the dopaminergic damage induced a decrease of LC basal neuron firing.…”

“…Similarly, we did not find significant changes in the response to reboxetine which is due to an increment in the level of noradrenaline in the synaptic cleft and a subsequent interaction with a 2 -adrenoceptors (Szabo & Blier, 2001a). Under control conditions, substantial amounts of dopamine are present in the LC (Kaehler et al 1999a, b ;Lin et al 2008), where it is used as the precursor of noradrenaline or as a neurotransmitter itself. Thus, dopamine and the dopaminergic agonist (+)3-PPP inhibit electrical activity of LC noradrenergic neurons (Cedarbaum & Aghajanian, 1977 ;Elam et al 1986 ;Guiard et al 2008a) whereas the dopaminergic antagonist, haloperidol, enhances it (Nilsson et al 2005).…”

Alpha-1 Adrenergic Receptors are Localized on Presynaptic Elements in the Nucleus Accumbens and Regulate Mesolimbic Dopamine Transmission

“…The a1ARs in this region could be activated by sparse local NE release or NE released from adjacent areas via volume transmission/ diffusion. DA, which has been shown to activate a1ARs under some conditions (eg, Lin et al, 2008), could be acting as an a1AR ligand in the NAc core.…”

What birdsong can teach us about the central noradrenergic system

“…There are also strong reciprocal connections between the locus coeruleus and the VTA (Swanson, 1982; Deutch, 1986; Meijas-Aponte et al, 2009) suggesting that these two systems might be tightly coupled. Locus coeruleus stimulation, for example, is able to modulate dopamine neuron activity in a noradrenergic receptor dependent manner (Arencibia-Albita et al, 2007; Grenhoff et al, 1995; Grenhoff and Svenson, 1989, 1993; Guiard et al, 2008; Paladini and Williams, 2004) and stimulation of dopaminergic areas causes norepinephrine to increase in the locus coeruleus (Deutch, 1986; Lin et al, 2008). The interactions between norepinephrine and dopamine also extend to reuptake mechanisms where the noradrenergic transporter can act as a reuptake mechanism for both norepinephrine and dopamine (Carboni et al, 1990, 2001; Moron et al, 2002; Torres et al, 2003).…”