Effects of sedatives on noradrenaline release from the medial prefrontal cortex in rats

Abstract

These data suggest that different clinical profiles observed with these two classes of sedatives may result from changes in noradrenaline release from the medial prefrontal cortex.

Subanesthetic Ketamine Treatment Promotes Abnormal Interactions between Neural Subsystems and Alters the Properties of Functional Brain Networks

“…The ketamineinduced alterations we have shown in the bipartite connectivity of these neural subsystems, as determined by GSVD analysis, parallel those we have previously reported using regional functional connectivity analysis (Dawson et al, 2013), that included a ketamine-induced enhancement of functional connectivity between selected neuromodulatory nuclei (DR and LC) and the PFC. As the neuromodulatory nuclei defined in this study included both the DR and the MR, sources of serotonergic innervation to the PFC, and the LC, a primary source of noradrenergic innervation to the PFC, the enhanced connectivity between these neural subsystems is consistent with the known ability of acute ketamine to profoundly enhance both serotonin (Lindefors et al, 1997;Amargos-Bosch et al, 2006) and noradrenaline levels in the PFC (Kubota et al, 1999). The altered connectivity of these neuromodulatory neurotransmitter systems may directly contribute to the disruption of PFCdependent processes by acute NMDA receptor blockade, a suggestion supported by the observation that the application of antagonist for the receptors of these neuromodulatory systems can attenuate the disruptive effects of NMDA receptor antagonists on PFC-dependent cognitive processes (Metzer et al, 2011;Mirjana et al, 2004), PFC physiology (Jentsch et al, 1998), and other translationally relevant behaviors (Bakshi and Geyer, 1997;Stuchlik et al, 2009).…”

Alpha-2 Adrenoceptor Activation Inhibits Phencyclidine-Induced Deficits of Spatial Working Memory in Rats

“…These data indicate that alpha-2 receptors tonically inhibit NMDA antagonist-induced deficits of cognition. Our hypothesis is that the increased release of noradrenaline that occurs after PCP administration (Bowers and Morton, 1994;Deutch et al, 1987;Kubota et al, 1999a) contributes directly to the cognitive deficits produced by the NMDA antagonist; this view is supported by the interaction between group (control vs DSP-4) and PCP dose, which was mediated by diminished PCP effects in animals (DSP-4 treated) with a compromised noradrenergic system. Using a match variant of the task employed here, Chudasama and Robbins (2004a) also provided evidence for an important neuromodulatory influence of dopamine D1 agonists in working memory performance.…”

“…Both PCP and ketamine dramatically increase noradrenaline release and turnover in brain (Bowers and Morton, 1994;Deutch et al, 1987;Kubota et al, 1999a;Lorrain et al, 2003;Rasmussen et al, 1991). In a recent study, Harkin et al (2001) demonstrated that the potent alpha-2 agonist, clonidine, strongly attenuated NMDA antagonist-induced hyperlocomotion in mice, while the potent alpha-2 receptor antagonist, yohimbine, produced opposite effects; Swanson and Schoepp (2003)reported similar effects of clonidine in rats.…”

Xenon inhalation increases norepinephrine release from the anterior and posterior hypothalamus in rats

“…Similarly, we reported previously that an anesthetic dose of ketamine also significantly increased norepinephrine release in the medial prefrontal cortex while an anesthetic dose of midazolam and propofol decreased the release of norepinephrine. 9 Therefore, some general anesthetics may increase norepinephrine release with anesthesia, while others will decrease it.…”

“…8,9 Briefly, the 10 µL samples were injected into ODS-C18 reverse-phase column (CA-5ODS, EICOM, Kyoto, Japan) maintained at 25C. The mobile phase was 0.1 M phosphate buffer containing 5% methanol and its flow was 220 µL·min -1 .…”