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Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults.
Schiltz JC, Sawchenko PE (2007) Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults. J Comp Neurol 502:455-467. doi: 10.1002/cne.21329
Summary: Interleukin-1 (IL-1) is one of the cytokines that mediates interactions between the immune system and the central nervous system. 380-ng injections of anti-DBH-SAP (Cat. #IT-03) were made into the paraventricular nucleus (PVH) of rats. Saporin (Cat. #PR-01) and mouse IgG-SAP (Cat. #IT-18) were used as controls. Lesioned animals demonstrated reduced responses to administration of IL-1, but restraint stress responses were left intact. The data suggest that ascending catecholaminergic projections mediate PVH response to IL-1.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01), Mouse IgG-SAP (Cat. #IT-18)
Hindbrain catecholamine neurons control multiple glucoregulatory responses.
Ritter S, Dinh TT, Li AJ (2006) Hindbrain catecholamine neurons control multiple glucoregulatory responses. Physiol Behav 89(4):490-500. doi: 10.1016/j.physbeh.2006.05.036
Summary: Glucose deficit evokes many responses in the brain. Recently these workers have been focusing on mechanisms eliciting glucoregulatory responses; the focus has settled on catecholaminergic neurons in the hindbrain. In a series of experiments rats received injections of anti-DBH-SAP (Cat. #IT-03) into epinephrine (E) and norepinephrine (NE) terminal areas of hypothalamus and spinal cord. The data suggest that E/NE neurons coordinate various components of the behavioral response to glucoprivation.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Selective depletion of cortical noradrenalin by anti-dopamine beta-hydroxylase-saporin impairs attentional function and enhances the effects of guanfacine in the rat.
Milstein JA, Lehmann O, Theobald DE, Dalley JW, Robbins TW (2007) Selective depletion of cortical noradrenalin by anti-dopamine beta-hydroxylase-saporin impairs attentional function and enhances the effects of guanfacine in the rat. Psychopharmacology (Berl) 190(1):51-63. doi: 10.1007/s00213-006-0594-x
Summary: Building on previous work, the authors examined the effect of cortical noradrenalin depletion on a reaction time task. Rats received 0.2 µg-intracortical infusions of anti-DBH-SAP (Cat. #IT-03), then were trained in a reaction time task. The effect of guanfacine, a selective a-2 adrenergic agonist was also tested in these animals. Lesioned rats were not impaired on the baseline task, but were slower and less accurate during high rate conditions. Guanfacine only affected the lesioned animals.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Role of catecholaminergic neurons of the caudal ventrolateral medulla in cardiovascular responses induced by acute changes in circulating volume in rats.
Pedrino GR, Maurino I, de Almeida Colombari DS, Cravo SL (2006) Role of catecholaminergic neurons of the caudal ventrolateral medulla in cardiovascular responses induced by acute changes in circulating volume in rats. Exp Physiol 91(6):995-1005. doi: 10.1113/expphysiol.2006.034611
Summary: Catecholaminergic neurons in the caudal ventrolateral medulla (CVLM) are thought to help regulate body fluid homeostasis and cardiovascular response due to changes in circulating volume. The authors injected 6.3 ng of anti-DBH-SAP (Cat. #IT-03) into the CVLM of rats, and measured several physiological parameters following an injection of hypertonic or isotonic saline. Data from the lesioned rats indicate that catecholaminergic neurons mediate the cardiovascular response to volume expansion or increases in sodium levels.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Noradrenergic inputs to the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus underlie hypothalamic-pituitary-adrenal axis but not hypophagic or conditioned avoidance responses to systemic yohimbine.
Banihashemi L, Rinaman L (2006) Noradrenergic inputs to the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus underlie hypothalamic-pituitary-adrenal axis but not hypophagic or conditioned avoidance responses to systemic yohimbine. J Neurosci 26(44):11442-11453. doi: 10.1523/JNEUROSCI.3561-06.2006
Summary: Yohimbine (YO) is an a2 adrenoceptor antagonist that increases transmitter release from adrenergic/noradrenergic (NA) neurons. The authors investigated whether NA inputs to the bed nucleus of the stria terminalis (BNST) were required for YO effects. After receiving 11 ng of anti-DBH-SAP (Cat. #IT-03) in the left and right BNST, rats displayed a marked decrease in the hypothalamic-pituitary-adrenal axis in response to YO administration.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
The effects of a norepinephrine reuptake blocker, atomoxotine, on an attentional set shifting impairment caused by prefrontal lesions
McGaughy JA (2006) The effects of a norepinephrine reuptake blocker, atomoxotine, on an attentional set shifting impairment caused by prefrontal lesions. Neuroscience 2006 Abstracts 749.17. Society for Neuroscience, Atlanta, GA.
Summary: There is substantial evidence to support the role of norepineprhine (NE) in selective attention. The NE system is hypothesized to maintain task-related attentional focus and allow shifts of attention (Aston-Jones and Cohen, 2005). These unique attentional functions correlate with changes in the firing patterns in locus coeruleus. Previous work in our lab has shown that NE lesions of the medial prefrontal cortex produces robust impairments in the ability of rats to perform an attentional set-shift, though acquisition of the attentional set and reinforcement reversal learning were spared. The current study assesses the effectiveness of atomoxotine, a NE reuptake blocker, in remediating these deficits. This drug is currently used in the treatment of attention deficit disorder and may restore balance to the noradrenergic system of the frontal cortex in these patients. Male, Long-Evans rats received lesions of the medial wall of the prefrontal cortex using dopamine beta-hydroxylase saporin (DBH-SAP) to produce selective noradrenergic deafferentation. The performance of DBH-SAP rats was compared to sham-lesioned (SHAM) rats in a test of attentional set-shifting after intraperitoneal injections of atomoxotine (0.0, 0.1,0.3, 0.9 mg/kg) 15 minutes prior to the test of attentional set-shifting. During the attentional set shifting task (Birrell and Brown 1999), rats were exposed to complex stimuli (texturized, scented pots filled with digging media). Initially rats were reinforced for focusing attention on one stimulus dimension, e.g. scent, during the tests of complex discriminations and reinforcement reversals. In tests of attentional set-shifting, subjects were required to inhibit attention to the previously reinforced dimension e.g. scent and learn that a new dimension e.g. texture predicted reinforcement.These results confirm that NE deafferentation of prefrontal cortex impairs the ability of rats to shift attention from the initially reinforced dimension to another dimension, e.g. when texture not odor now predicts reinforcement. Low doses of atomoxotine ameliorate the set-shifting impairments of DBH-SAP rats but hindered the performance of SHAM rats. These data suggest that shifts of attentional set require an optimal level of release of NE in the frontal cortex with both high and low levels of NE causing impairments in these abilities.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Noradrenergic nuclei involved in sensory input during mating project to the ventromedial hypothalamus and are involved in mating-induced pseudopregnancy in female rats
Northrop LE, Erskine MS (2006) Noradrenergic nuclei involved in sensory input during mating project to the ventromedial hypothalamus and are involved in mating-induced pseudopregnancy in female rats. Neuroscience 2006 Abstracts 661.23. Society for Neuroscience, Atlanta, GA.
Summary: The ventrolateral region of the ventromedial hypothalamus (VMHvl) is known to control female sexual receptivity through the activity of ovarian steroids in the female rat. These receptors are thought to aide in the steroid-dependent facilitation of the lordosis posture. Besides harboring estrogen and progesterone receptors, dense numbers of noradrenergic receptors are also present in the VMHvl. Previous research has shown that norepinephrine is released in significant amounts within the VMHvl after a female receives vaginocervical stimulation (VCS). At the time of mating, the vaginocervical sensory input travels from the brainstem, through the ventral noradrenergic bundle (VNAB), and finally to the VMH. Sufficient amounts of VCS are necessary for inducing twice daily prolactin surges, which are required for the initiation of pseudopregnancy (PSP). To distinguish whether these cells play a role in mating-induced PSP, they were selectively lesioned using the immunotoxin anti-dopamine-β-hydroxylase-saporin (DBH-SAP) 10 days prior to mating. Females were given bilateral VMHvl infusions of either 60ng/0.6µl of DBH-SAP or 2ng/0.6µl of IGG-SAP (non-specific control). Ten days following infusion on proestrous, females received one of two treatments: no VCS (home cage), or a sufficient amount of VCS (15 intromissions from males) to induce PSP. PSP was measured using vaginal smears and serum PRL concentrations. The next witnessed proestrous day after mating, females were mated again with the same type of stimulus as previously administered and perfused 90 min later. The brainstems were cut in 30µm sections, and ICC was used to visualize DBH and FOS immunoreactivity (IR). FOS-IR and DBH-IR cells were counted in the A2 and A1 cell regions, components of the VNAB. DBH-SAP infused females that received 15I showed 50% induction of PSP whereas IGG-SAP (15I) females showed 100% induction of PSP. None of the home cage rats became PSP . VMHvl DBH-SAP infusions significantly decreased DBH/FOS-IR expression in A2 and A1 nuclei, as well as decreased expression in DBH-IR in A2 nuclei compared to IGG-SAP infused females. Our results show that A1 and A2 noradrenergic cells which innervate the VMHvl are required for initiation of P/PSP.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Catecholaminergic afferents are required for hypothalamic parvicellular paraventricular neurons to transduce signals associated with hypoglycemia into p44/42 MAP kinase phosphorylation events
Rapp KL, Khan AM, Watts AG (2006) Catecholaminergic afferents are required for hypothalamic parvicellular paraventricular neurons to transduce signals associated with hypoglycemia into p44/42 MAP kinase phosphorylation events. Neuroscience 2006 Abstracts 355.9. Society for Neuroscience, Atlanta, GA.
Summary: Hypoglycemia activates CRH neuroendocrine neurons in the hypothalamic paraventricular nucleus (PVH), thereby rapidly elevating plasma ACTH and corticosterone concentrations. Hindbrain-originating catecholaminergic (CA) neurons projecting to the PVH facilitate ACTH release after insulin-induced hypoglycemia; however, the intracellular signaling mechanisms that CRH neurons use to transduce CA signals into secretogogue function are unknown. We have previously shown that p44 and/or p42 MAP kinases (ERK1/2) are phosphorylated in CRH neurons after 2-deoxy-D-glucose challenge (Endoc. v145:351, 2004). We now ask: Are hindbrain-originating CA projections to the PVH essential for ERK1/2 phosphorylation in response to insulin-induced hypoglycemia? Male Sprague-Dawley rats received acute bilateral PVH microinjections of either saporin toxin conjugated (DSAP) to an antiserum against dopamine beta hydroxylase (DBH) or conjugated to a non-targeted mouse IgG (control mIgG-SAP), were fitted with jugular catheters, and allowed to recover. On the day of testing, plasma glucose was measured just before the onset of hypoglycemia (induced via insulin bolus [2U/kg, i.v.]) and then 10 and 30 min thereafter. Rats were then anesthetized and transcardially perfused. Brain tissue processed for dual immunofluorescence using antibodies raised against DBH and phospho-ERK1/2 was visualized by confocal microscopy. Baseline plasma glucose levels did not differ significantly between groups (5.66 ± 0.26 mM), but were significantly reduced in each group when compared to baseline after 10 (1.48 ± 0.12 mM) and 30 (1.92 ± 0.12 mM) minutes. DSAP rats displayed marked loss of DBH immunostaining in the PVH relative to controls, with concomitant loss of phospho-ERK1/2 immunostaining within the parvicellular PVH. Further analysis was performed to address the effect of DSAP on DBH staining and ERK1/2 recruitment in the hindbrain and arcuate nucleus. Our results confirm that phosphorylation of ERK1/2 in parvicellular PVH after insulin-induced hypoglycemia requires intact CA afferent innervation. These data contribute to our understanding of how intracellular signaling is regulated in parvicellular PVH neurons. They also underscore an emerging importance of CA afferents for mediating neuroendocrine responses to systemic alterations in glucose.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Glucoprivation enhances dopamine-beta-hydroxylase gene expression in hindbrain catecholamine cells
Li A, Ritter S (2006) Glucoprivation enhances dopamine-beta-hydroxylase gene expression in hindbrain catecholamine cells. Neuroscience 2006 Abstracts 359.12. Society for Neuroscience, Atlanta, GA.
Summary: Hindbrain catecholaminergic neurons are key participants in systemic glucoregulation. Using in situ hybridization, we investigated the effects of glucoprivation on gene expression of dopamine-beta-hydroxylase (DBH), a key enzyme for catecholamines synthesis, to further define the catecholamine subpopulation activated by glucoprivation. Glucoprivation induced by systemic injection of the glycolytic inhibitor, 2-deoxy-D-glucose (2DG, 250 mg/kg body weight) increased total DBH mRNA expression in caudal ventrolateral medullary cell groups (namely, A1, the A1/C1 overlap, and middle C1) from 6 – 49 times control levels. In retrofacial C1, A5 and A7 no enhancement was observed. In the dorsomedial medulla, DBH mRNA hybridization signal was modestly increased (tripled) in cell group A2, but not in the area postrema. Furthermore, a previous hypothalamic microinjection of the retrogradely transported immunotoxin, anti-DBH-saporin, profoundly reduced DBH-positive cells in hindbrain, and abolished the 2DG-stimulated increases of DBH mRNA expression in the caudal ventrolateral medulla and A2 regions. The strong glucoprivation-induced enhancement of DBH gene expression in particular cell populations is consistent with the demonstrated importance of catecholaminergic neurons for glucoregulation and provides further evidence for functional specialization within the catecholamine cell population.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Lesions of the dorsal noradrenergic bundle impair attentional set-shifting in the rat
Tait DS, Brown VJ, Farovik A, Theobald DE, Dalley JW, Robbins TW (2006) Lesions of the dorsal noradrenergic bundle impair attentional set-shifting in the rat. Neuroscience 2006 Abstracts 264.4. Society for Neuroscience, Atlanta, GA.
Summary: Rats with medial prefrontal cortex (mPFC) lesions are impaired in attentional set shifting (Birrell and Brown, 2000, J Nsci, 20:4320-4324). The mPFC receives multiple projections, but norepinephrine (NE) has previously been reported to modulate attention by its action in the mPFC (for review see Dalley et al., 2004, Nsci Biobeh Rev, 28:771-784), including shifting attentional set. Indeed, there is recent evidence that increasing NE in the mPFC by autoreceptor antagonism improves set-shifting performance in rats (Lapiz and Morilak, 2006, Nsci, 137:1039-1049). Furthermore, reduction of prefrontal NE by infusion of anti-DBH-saporin into PFC has been shown to impair attentional set-shifting in rats (Eichenbaum et al., 2003, SfN Abstract 940.7). The main source of noradrenergic input to the mPFC is from locus coerulus via the dorsal noradrenergic bundle (DNAB). This study examined the effect of lesions of the DNAB on the acquisition, maintenance and shifting of attentional set. Eleven male Lister-hooded rats received bilateral DNAB lesions by infusion of 6-hydroxydopamine (4μg in 2μl each side) at (nosebar -2.4mm) AP -6.0mm, ML ±1.0mm, DV -5.0mm (from dura). Twelve control rats received injections of vehicle. Rats learned to dig for bait in bowls then learned two simple discriminations – based on the bowls odor or the digging substrate – to a criterion of six consecutive correct trials. The next day, a series of discriminations tested acquisition of novel discriminations (both intra (ID) and extradimensional (ED)) and reversal learning. Trials to criterion, incorrect trials and dig-latencies were recorded and analysed. At conclusion of testing, brain tissue samples were analysed for NE content by HPLC-ECD. All rats required more trials to reverse previously learned associations, and to learn new discriminations when attentional refocusing was required (ED shift). Rats with DNAB lesions were unimpaired at reversal stages, but were impaired at the ED acquisition stage. Lesioned rats showed reductions of NE levels in mPFC (up to 95% in the infralimbic region, 89% in the prelimbic region and 93% in cingulate area Cg1). These data provide further evidence for the role of NE in attentional set-shifting, and combine with previous data to elucidate the mechanisms by which mPFC mediates attentional set-shifting in the rat.
Related Products: Anti-DBH-SAP (Cat. #IT-03)