Ventral Noradrenergic Bundle Lesions Research Articles

The Impact of Ventral Noradrenergic Bundle Lesions on Increased IL-1 in the PVN and Hormonal Responses to Stress in Male Sprague Dawley Rats

The impact of acute stress on inflammatory signaling within the central nervous system is of interest because these factors influence neuroendocrine function both directly and indirectly. Exposure to certain stressors increases expression of the proinflammatory cytokine, Il-1β in the hypothalamus. Increased IL-1 is reciprocally regulated by norepinephrine (stimulatory) and corticosterone (inhibitory), yet neural pathways underlying increased IL-1 have not been clarified. These experiments explored the impact of bilateral lesions of the ventral noradrenergic bundle (VNAB) on IL-1 expression in the paraventricular nucleus of the hypothalamus (PVN) after foot shock. Adult male Sprague Dawley rats received bilateral 6-hydroxydopamine lesions of the VNAB (VNABx) and were exposed to intermittent foot shock. VNABx depleted approximately 64% of norepinephrine in the PVN and attenuated the IL-1 response produced by foot shock. However, characterization of the hypothalamic-pituitary-adrenal response, a crucial prerequisite for interpreting the effect of VNABx on IL-1 expression, revealed a profound dissociation between ACTH and corticosterone. Specifically, VNABx blocked the intronic CRH response in the PVN and the increase in plasma ACTH, whereas corticosterone was unaffected at all time points examined. Additionally, foot shock led to a rapid and profound increase in cyclooxygenase-2 and IL-1 expression within the adrenal glands, whereas more subtle effects were observed in the pituitary gland. Together the findings were the 1) demonstration that exposure to acute stress increased expression of inflammatory factors more broadly throughout the hypothalamic-pituitary-adrenal axis; 2) implication of a modest role for norepinephrine-containing fibers of the VNAB as an upstream regulator of PVN IL-1; and 3) suggestion of an ACTH-independent mechanism controlling the release of corticosterone in VNABx rats.

Differential effects of hypothalamic catecholamine depletion on the release of arginine vasopressin and CRF-41 into hypothalamo-hypophyseal portal blood

The effects of 6-hydroxydopamine lesions of the ventral noradrenergic bundle (VNAB) and of intracerebroventricular 6-hydroxydopamine on hypothalamo-hypophyseal portal blood (HPB) concentrations of arginine vasopressin (AVP), corticotrophin releasing factor (CRF-41), and noradrenaline have been investigated. VNAB lesions and intracerebroventricular 6-hydroxydopamine caused a reduction of HPB CRF-41 concentration, while AVP remained unchanged. HPB noradrenaline concentration was reduced in animals treated with lateral ventricular 6-hydroxydopamine, but was unchanged in VNAB lesioned animals. Our results suggest differential effects of noradrenaline on the release of AVP and CRF-41 into HPB.

Effect of ventral noradrenergic bundle lesions on concentrations of monoamine neurotransmitters and metabolites in several discrete areas of the rat brain.

1. The effects of radiofrequency lesions of the ventral noradrenergic bundle (VNB) on monoamine and metabolite concentrations in several discrete areas of the rat hypothalamus were examined. Monoamines and metabolites were analyzed utilizing high-performance liquid chromatography coupled with electrochemical detection. 2. VNB lesions decreased the concentrations of norepinephrine (NE) and 3-methoxy-4-hydroxyphenylethylene glycol in all areas examined except in the ventromedial nucleus (VMN). Dopamine and 3,4-dihydroxyphenylacetic acid concentrations were selectively decreased in the dorsomedial nucleus (DMN) and also slightly decreased in the medial forebrain bundle following VNB lesions. Serotonin and 5-hydroxyindole-3-acetic acid concentrations were not altered by VNB lesion in any area examined. 3. The results indicate that the NE innervation to the hypothalamus is extensive and that NE in the VMN may not be derived from the VNB. The source of the DA innervation to the DMN may be located in or pass through the area affected by the VNB lesion.

Modulation of oxytocin secretion by ascending nordrenergic pathways: sexual dimorphism in rats

We have investigated the role of ascending noradrenergic pathways in the control of oxytocin (OT) and arginine-vasopressin (AVP) secretion during acute immobilization stress in male and female rats. 6-Hydroxydopamine-induced lesions of the ventral noradrenergic bundle (VNAB) resulted in a selective depletion of hypothalamic noradrenaline content. In sham-lesioned rats plasma levels of OT were raised following stress, the response being significantly greater in female compared with male animals. VNAB lesions were not associated with altered responses in female rats, whereas lesioned males exhibited markedly elevated OT stress responses. AVP secretion was not modulated in VNAB-lesioned rats of either sex. The results provide functional evidence of a sexually dimorphic inhibitory role of the VNAB in the control of OT secretion.

The corticotropin-releasing factor release in rat hypophysial portal blood is mediated by brain catecholamines.

In order to study the involvement of the hypothalamic corticotropin-releasing factor (CRF) in catecholamine-induced adrenocorticotropin (ACTH) secretion, we have measured CRF levels in rat hypophysial portal blood (HPB) after the pharmacological destruction of the ventral noradrenergic bundle (VNAB), using 6-hydroxydopamine (6-OHDA) stereotaxically injected into the VNAB. CRF levels in HPB were measured by radioimmunoassay, and the effects of 6-OHDA injection were controlled by the determination of catecholamine concentrations in the total hypothalamus. VNAB lesions induced a dramatic decrease in norepinephrine and epinephrine hypothalamic concentration. The CRF levels in HPB were also significantly reduced. These results suggest that central catecholamines exert a direct stimulatory control on the CRF release and play a major role in stress-induced ACTH secretion.

Contrasting interactions of the locus coeruleus as compared to the ventral noradrenergic bundle with CNS and pituitary pools of vasopressin, dynorphin and related opioid peptides in the rat

The present study examines the influences of selective destruction of the locus coeruleus (LC) or of the ventral noradrenergic bundle (VB) upon discrete CNS and pituitary pools of vasopressin, dynorphin and related opioid peptides in the rat. The selectivity of the lesions was indicated by the fact that destruction of the LC strongly depressed levels of noradrenaline in the cortex in contrast to the hypothalamus, whereas destruction of the VB decreased noradrenaline in hypothalamus but not cortex. Rats sustaining VB lesions displayed a parallel depletion neurointermediate, but not anterior, lobe levels of immunoreactive- (irdynorphin 1–17 (DYN), ir-DYN 1–8, ir-α-neo-endorphin (ir-α-NE) and ir-vasopressin (ir-VP) whereas those of ir-Met-enkephalin (ir-ME) were unaffected. In the hypothalamus, the content of ir-DYN and ir-VP tended to rise and that of ir-DYN 1–8 and ir-α-NE was significally elevated, whereas that of ir-ME was not altered. LC destruction failed, in contrast, to modify levels of ir-VP, ir-DYN, ir-DYN 1–8, ir-α-NE or ir-ME in any of the above structure. It was found to, however, result in depression in levels of ir-DYN and ir-α-NE, but not of ir-ME or ir-VP, in both the hippocampus and striatum whereas VB lesions were, in this respect, ineffective. Further, in the spinal cord, LC lesions resulted in a significant elevation in levels of ir-DYN and ir-α-NE in comparison to those of ir-DYN 1–8, ir-VP and ir-ME. Neither type of lesion significantly altered the content of any opioid peptide examined in thalamus, cortex, septum or midbrain. These data indicate that: (1) the LC as compared to the VB interact differently with discrete pools of ir-DYN, ir-DYN 1–8, ir-α-NE and ir-VP in brain, pituitary and spinal cord; (2) it is the VB rather than the LC which modulates the activity of magnocellular neurones projecting to the neural lobe of the pituitary; (3) ir-DYN, ir-DYN 1–8 and ir-α-NE are, in all tissues, regulated independently of ir-ME; (4) levels of ir-DYN, ir-DYN 1–8 and ir-α-NE are co-regulated with those of ir-VP in the hypothalamus-neural obbe axis but not in extrahypothalamic brain tissues for the spinal cord; and (5) DYN, DYN 1–8 and α-NE might, in certain cases, be modulated differentially of one another, possibly reflecting alterations in precursor processing.

Changes in body weight and food-related behaviour induced by destruction of the ventral or dorsal noradrenergic bundle in the rat

Three experiments contrasted the effects of 6-hydroxydopamine-induced lesions of the ventral noradrenergic and dorsal noradrenergic projections, predominantly to hypothalamus and cortex, respectively, upon body weight changes and food-related behaviour in the rat. In general, ventral noradrenergic bundle lesions enhanced weight gain and these effects were exaggerated by the provision of palatable cheese to the standard chow diet. In contrast, lesions of the dorsal noradrenergic bundle produced minor changes in body weight. Associated with the effects of ventral noradrenergic bundle lesions were hyperphagia, enhanced suppression of intake of food adulterated with quinine, (at high concentration), a small attenuation of food neophobia, and enhanced acquisition, but not performance, of the eating response to tail-pinch stimulation. These ventral noradrenergic bundle lesions failed to alter basal activity levels, amphetamine anorexia or the diurnal pattern of eating or activity. In contrast, lesions of the dorsal noradrenergic bundle did not produce either hyperphagia or enhanced rejection of food adulterated with quinine. However, there was a strong attenuation of food neophobia and a retarded acquisition (but unimpaired performance) of eating in response to tail-pinch stimulation. The results are discussed in connection with previous studies of ventral and dorsal noradrenergic bundle lesions, with the effects of ventromedial hypothalamic lesions and with the underlying behavioural and physiological processes that mediate these contrasting effects of different neuroanatomical patterns of central noradrenaline depletion.

Increased weight gain and reduced activity in brown adipose tissue produced by depletion of hypothalamic noradrenaline

The effects of hypothalamic noradrenaline depletion produced by injection of 6-hydroxydopamine (6-OHDA) into the vicinity of cell bodies of the ventral noradrenergic bundle (VNAB) on weight gain, food intake and brown adipose tissue (BAT) activity (as measured by GDP binding in BAT mitochondria), were examined in rats at two different ages and under two different dietary conditions (chow and chow plus palatable cheese). VNAB lesions enhanced weight gain in the chow plus cheese diet conditions and produced small increases in feeding. These effects were parallelled by reductions in BAT activity in the VNAB group, suggesting a reduced capacity for dietary thermogenesis which may contribute to the significant overweight.

Rotational behavior produced by unilateral ventral noradrenergic bundle lesions: Evidence for a noradrenergic-dopaminergic interaction in the brain

In this study the effect of unilateral electrocoagulation of the ventral noradrenergic bundle (VB) on rotational behavior produced by dopaminergic agonists was investigated. Unilateral lesions to the VB produced a decrease in the concentration of noradrenaline but not dopamine, serotonin or 5-hydroxyindoleacetic acid (5-HIAA) in the ipsilateral part of the forebrain. These lesions produced also strong and dose-dependent preference for ipsilateral rotation after systemic injection of apomorphine or amphetamine. The results are discussed in terms of possible interaction between noradrenergic and dopaminergic systems and it is proposed that the VB plays a regulatory role in the function of brain nigro-striatal dopaminergic system.

Unilateral blockade of the dorsal ascending noradrenergic bundle and septal elicitation of hippocampal theta rhythm

Unilateral blockade of the dorsal ascending noradrenergic bundle was produced by injections of procaine or of 6-hydroxydopamine. The threshold current of septal stimulation required to drive the hippocampal theta rhythm was then investigated at frequencies between 5.9 and 10.0 Hz. With both types of blockade the threshold-frequency function showed a normal 7.7 Hz minimum ipsilaterally and an abolition of the minimum contralaterally. Ventral noradrenergic bundle lesions had no effect. Septal elicitation of hippocampal theta rhythm may, therefore, be dependent on a noradrenergic mechanism controlling aspects of the theta rhythm, e.g. interhemispheric balance, which would not be obvious in ordinary spontaneous records.