The release of noradrenaline in the locus coeruleus and prefrontal cortex studied with dual-probe microdialysis

Pudovkina, Olga L.; Kawahara, Yukie; Vries, J. B. De; Westerink, Ben H.C.

doi:10.1016/s0006-8993(01)02553-7

Cited by 75 publications

(50 citation statements)

References 34 publications

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“…These disruptions likely result from specific actions within the LC, because infusions of BET even 250 mm away from the active drug zone had no effect, co-infusion of the a2 autoreceptor agonist clonidine (which reliably and markedly reduces activity of LC neurons and downstream NE release including in unanesthetized rats (Berridge et al, 1993;Pudovkina et al, 2002;Pudovkina et al, 2001;Van Gaalen et al, 1997)) prevented the BET-induced deficit, and systemic administration of the a1 NE antagonist prazosin completely reversed the PPI deficit following peri-LC BET. The same manipulation that disrupted PPI failed to alter locomotion, grooming, rearing, or ingestive behaviors, indicating that LC-mediated PPI disruption is not the nonspecific consequence of generalized motor effects.…”

Section: Discussionmentioning

confidence: 99%

“…Are LC-mediated PPI deficits specific to NE transmission? First, to confirm that the peri-LC BET effect was due to activation of LC neurons, we determined whether co-infusion of clonidine, an a2 NE (autoreceptor) agonist that significantly reduces activity of LC neurons and NE release in terminal regions after peri-LC delivery in anesthetized or awake rats (Berridge et al, 1993;Pudovkina et al, 2002;Pudovkina et al, 2001;Van Gaalen et al, 1997), prevented the peri-LC BET-induced PPI deficit. Thus, rats (N ¼ 7) received a 'cocktail' of clonidine (0 or 1500 ng) and BET (0 or 500 ng) into peri-LC immediately before startle/ PPI testing; each rat received all the four drug combinations in a counterbalanced order over four test days.…”

Section: Experimental Designmentioning

confidence: 99%

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Pharmacological Stimulation of Locus Coeruleus Reveals a New Antipsychotic-Responsive Pathway for Deficient Sensorimotor Gating

Alsene

Bakshi

2011

Neuropsychopharmacol

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Surprisingly little is known about the modulation of core endophenotypes of psychiatric disease by discrete noradrenergic (NE) circuits. Prepulse inhibition (PPI), the diminution of startle responses when weak prestimuli precede the startling event, is a widely validated translational paradigm for information-processing deficits observed in several mental disorders including schizophrenia, Tourette's syndrome, and post-traumatic stress disorder (PTSD). Despite putative NE disturbances in these illnesses, NE regulation of PPI remains poorly understood. In these studies, regulation of PPI by the locus coeruleus (LC), the primary source of NE to forebrain, was evaluated in rats using well-established protocols to pharmacologically activate/inactivate this nucleus. The ability of drugs that treat deficient PPI in these illnesses to reverse LC-mediated PPI deficits was also tested. Stimulation of LC receptors produced an anatomically and behaviorally specific deficit in PPI that was blocked by clonidine (Cataprese, an a2 receptor agonist that reduces LC neuronal firing after peri-LC delivery), a postsynaptic a1 NE receptor antagonist (prazosin), and second-generation antipsychotics (olanzapine, seroquel), but not by drugs that antagonized dopamine-1 (SCH23390), dopamine-2 (the first-generation antipsychotic Haloperidol), or serotonin-2 receptors (ritanserin). These results indicate a novel substrate in the regulation of PPI and reveal a novel functional role for the LC. Hence, a hyperactive LC-NE system might underlie a deficient sensorimotor gating endophenotype in a subset of patients suffering from psychiatric illnesses including schizophrenia, Tourette's syndrome, and PTSD, and the ability to normalize LC-NE transmission could contribute to the clinical efficacy of certain drugs (Cataprese, prazosin, and second-generation antipsychotics) in these conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

Pharmacological Stimulation of Locus Coeruleus Reveals a New Antipsychotic-Responsive Pathway for Deficient Sensorimotor Gating

Alsene

Bakshi

2011

Neuropsychopharmacol

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“…Novelty provides a key trigger for arousal and it is therefore not surprising to find that LC/NA activity occurs strongly in response to novel stimuli (Kitchigina, 1997,McQuade, et al, 1999,Pudovkina, et al, 2001,Vankov, et al, 1995. Human genetic studies have shown that processing novel stimuli, as measured by EEG ERP P300 responses, is associated with genes influencing noradrenergic availability (Liu, et al, 2009).…”

Section: Response To Noveltymentioning

confidence: 99%

A right hemisphere role in cognitive reserve

Robertson

2014

Neurobiology of Aging

131

153

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High levels of education, occupational complexity and/or premorbid intelligence are associated with lower levels of cognitive impairment than would be expected from a given brain pathology. This has been observed across a range of conditions including Alzheimer's Disease (Roe, et al., 2010), stroke (Ojala-Oksala, et al., 2012), traumatic brain injury (Kesler, et al., 2003), and penetrating brain injury (Grafman, 1986). This cluster of factors, which seemingly protect the brain from expressing symptoms of damage, has been termed 'cognitive reserve' (Stern, 2012). The current review considers one possible neural network which may contribute to cognitive reserve. Based on evidence that the neurotransmitter noradrenaline mediates cognitive reserve's protective effects (Robertson, 2013) this review identifies the neurocognitive correlates of noradrenergic (NA) activity. These involve a set of inter-related cognitive processes (arousal, sustained attention, response to novelty and awareness) with a strongly right hemisphere, fronto-parietal localization, along with working memory which is also strongly modulated by NA. It is proposed that this set of processes is one plausible candidate for partially mediating the protective effects of cognitive reserve. In addition to its biological effects on brain structure and function, NA function may also facilitate networks for arousal, novelty, attention, awareness and working memory which collectively provide for a set of additional, cognitive, mechanisms that help the brain adapt to age-related changes and disease. It is hypothesized that to the extent that the lateral surface of the right prefrontal lobe and/or the right inferior parietal lobe maintain structural (white and grey matter) and functional integrity and connectivity, cognitive reserve should benefit and behavioral expression of pathological damage should thus be mitigated.

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“…Interestingly, increased norepinephrine release after CRF administration is observed after substantial delays (Palamarchouk et al, 2002), and the administration of clonidine, which reduces norepinephrine release by acting as an agonist at presynaptic inhibitory a 2 receptor (Pudovkina et al, 2001) and is used as an aid for smoking cessation (Frishman, 2007), into the BNST abolishes the LES effect under baseline conditions (ie no nicotine withdrawal; Schweimer et al, 2005). Therefore, we speculate that CRF may be released during early nicotine withdrawal, which could lead to a delayed norepinephrine effect, which may in turn potentiate LES.…”

Section: Spontaneous Nicotine Withdrawal In Rats S Jonkman Et Almentioning

confidence: 99%

Spontaneous Nicotine Withdrawal Potentiates the Effects of Stress in Rats

Jonkman

Risbrough

Geyer

et al. 2007

Neuropsychopharmacol

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Anxiety is a common symptom of nicotine withdrawal in humans, and may predict an inability to abstain from cigarette smoking. It is not clear if self-reports of anxiety during abstinence reflect increased baseline anxiety and/or increased responses to exogenous stressors. We hypothesized that nicotine withdrawal selectively exacerbates reactivity to aversive stimuli in rodents. Here, we investigated the effect of withdrawal from chronic nicotine administration (3.16 mg/kg per day base, delivered via subcutaneous osmotic minipumps) in the light-enhanced startle (LES) test in Wistar rats. In this procedure, baseline startle responding in the dark is compared to startle responding when the chamber is brightly lit. Bright illumination is aversive for rats and potentiates the startle response. Hence, this procedure allows comparisons of withdrawal effects on startle reactivity between relatively neutral and stressful contexts. We found that spontaneous nicotine withdrawal (24 h post-pump removal) did not influence baseline startle responding, but produced a selective increase in LES. Precipitated nicotine withdrawal through injections of one of two nicotinic acetylcholine receptor (nAChR) antagonists, dihydro-b-erythroidine hydrobromide (DHbE: 0, 1.5, 3, or 6 mg/kg) or mecamylamine (0, 1, 2, or 4 mg/kg), did not influence baseline startle responding or LES. These results suggest that spontaneous nicotine withdrawal selectively potentiates responses to anxiogenic stimuli, but does not by itself produce a strong anxiogenic effect. These findings support the hypothesis that nicotine withdrawal exacerbates stress responding, and indicate LES may be a useful model to examine withdrawal effects on anxiety.

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The release of noradrenaline in the locus coeruleus and prefrontal cortex studied with dual-probe microdialysis

Cited by 75 publications

References 34 publications

Pharmacological Stimulation of Locus Coeruleus Reveals a New Antipsychotic-Responsive Pathway for Deficient Sensorimotor Gating

Pharmacological Stimulation of Locus Coeruleus Reveals a New Antipsychotic-Responsive Pathway for Deficient Sensorimotor Gating

A right hemisphere role in cognitive reserve

Spontaneous Nicotine Withdrawal Potentiates the Effects of Stress in Rats

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