Biomedical subjects

M H Millan

Publications and source records attributed to M H Millan.

46 records · Page 3Linked to original sources

PubMed1983

Response of brain and pituitary pools of dynorphin as compared to vasopressin to acute stress in the rat.

5 min foot-shock resulted in an elevation in levels of immunoreactive (ir)-dynorphin (DYN) and ir-vasopressin (VP) in the hypothalamus whereas their levels were not significantly modified in the neurointermediate pituitary. In the anterior pituitary, however, a fall in ir-DYN in the absence of any change in ir-VP was detected. Further, in the thalamus and medulla/pons, respectively, a decrease and increase in levels of ir-VP was observed whilst the content of ir-DYN therein was not significantly affected. These findings support the concept of a common origin and co-modulation of DYN and VP in the hypothalamic-neural lobe axis and that, extrinsic to this, DYN and VP are localized and modulated independently of each other.

Animals↗

PubMed1983

Evidence for a role of the ventro-medial posterior hypothalamus in nociceptive processes in the rat.

Bilateral, radio-frequency destruction of the ventro-medial posterior hypothalamus (VMPH) resulted, as compared to sham-operated and control rats and evaluated in the tail-flick and vocalization tests, in a significant decrease in basal nociceptive threshold on day 4 post-surgery. By day 12, however, no significant difference between sham and lesioned rats was seen. At this time the antinociception elicited by either acute foot-shock or cold-water-immersion stress was profoundly attenuated. The antinociceptive response to various doses of morphine was not, in contrast, diminished. As established by use of radioimmunoassay, these lesions did not significantly alter hypothalamic levels of beta-endorphin, met-enkephalin, dynorphin or alpha-neo-endorphin. They did, however, produce a pronounced and significant fall in the hypothalamic content of substance P. These data are indicative that the VMPH may, via a mechanism not involving endorphins, be of importance in the determination of basal nociceptive threshold and in the generation of stress-, but not morphine-, evoked antinociception. The relationship of these findings to the interconnections of the VMPH, and to the possible significance of substance P and the pituitary in nociceptive processes, is discussed.

Animals↗

PubMed1983

Contribution of the supra-optic nucleus to brain and pituitary pools of immunoreactive vasopressin and particular opioid peptides, and the interrelationships between these, in the rat.

Discrete, bilateral, radiofrequency destruction of the supra-optic nucleus resulted in a parallel fall in levels of immunoreactive (ir) dynorphin (DYN), ir-alpha-neo-endorphin (alpha-NE) and ir-vasopressin (VP) in the hypothalamus, neurointermediate lobe (NIL) of the pituitary and septum of rats, whereas in the medulla/pons, midbrain and anterior lobe (AL), levels of theses peptides were not significantly changed. The content of ir-beta-endorphin (beta-endorphin (beta-EP) was, in contrast, elevated in the hypothalamus and unchanged in the NIL and AL, while that of ir-met-enkephalin (ME) was modified in neither the hypothalamus nor medulla/pons. As evaluated in lesioned and sham rats, collectively, hypothalamic levels of ir-DYN, ir-alpha-NE and ir-vP were positively correlated with their counterparts in the NIL but not, with the exception of ir-VP, with those in the AL. Ir-beta-E did not show these relationships. Within the NIL and in the hypothalamus, levels of ir-DYN, ir-alpha-NE and ir-VP were positively correlated with each other and independent of those of ir-beta-EP and ir-ME. In the ALK and other brain tissues, however, only those of ir-DYN and ir-alpha-NE were positively and significantly correlated in contrast to ir-VP. Further, across all structures, although the ratio of levels of ir-alpha-NE to ir-DYN was quite constant, that of ir-VP to ir-DYN varied enormously. These data indicate that: (1) the supra-optic nucleus may contribute to NIL, hypothalamic and septal but not to AL, midbrain or medulla/pons pools of ir-VP, ir-DYN and ir-alpha-NE, and that it interacts with those of ir-beta-EP in the hypothalamus. (2) in the NIL and hypothalamus, ir-DYN, ir-alpha-NE and ir-VP are, as compared to ir-beta-EP and ir-ME, closely interrelated. (3) AL pools of DYN and ir-alpha-NE are closely coupled but, in contrast to NIL pools, not related to ir-VP and independent of the hypothalamus. (4) Extrahypothalamic brain pools of ir-DYN and ir-alpha-NE may be not related to ir-VP. The possible existence of ir-DYN and ir-alpha-NE independently or ir-vP in the AL and extrahypothalamic nervous tissue is discussed.

Animals↗

PubMed1982

Independent origin and modulation of vasopressin as compared to dynorphin and alpha-neo-endorphin in the medulla-pons of the rat.

Bilateral, radiofrequency destruction of the hypothalamic paraventricular nucleus resulted in a pronounced depression in levels of immunoreactive (ir-) vasopressin (VP) in the medulla-pons of rats. The contents of ir-dynorphin1-17 (DYN), ir-DYN1-8 and ir-alpha-neo-endorphin (alpha-NE) therein were not, in contrast, affected. Exposure of naive rats to acute foot-shock stress was associated with an elevation in levels of ir-VP in the medulla-pons whereas those of ir-DYN, ir-DYN1-8 and ir-alpha-NE were not significantly altered. The data indicate that the paraventricular nucleus is a major source of ir-VP but not of ir-DYN, ir-DYN1-8 or ir-alpha-NE in the medulla-pons, and that these pools of ir-VP, in contrast to those of ir-DYN, ir-DYN1-8 and ir-alpha-NE, are involved in the response to stress. It is concluded that ir-DYN, ir-DYN1-8 and ir-alpha-NE exist in (a) neuronal network(s) independent of that of ir-VP in the medulla-pons of the rat.

Animals↗

PubMed1982

The influence of selective adeno- and neurointermedio-hypophysectomy upon plasma and brain levels of beta-endorphin and their response to stress in rats.

Selective ablation of the anterior lobe (AL) of the pituitary led to a fall in basal plasma levels of beta-endorphin immunoreactivity (beta-EI) at 3 and 20 weeks post-surgery (p.s.). Further, the stress-evoked rise in circulating levels of beta-EI was abolished. This operation did, however, severely deplete the beta-EI content of the neurointermediate lobe (NIL). Removal of the NIL did not, in contrast, decrease the beta-EI content of the AL but depressed basal plasma levels of beta-EI at 3 weeks p.s. and attenuated, but did not abolish, the increase in these elicited by stress at both 3 and 20 weeks p.s. In rats not possessing a NIL, a secretion of beta-EI into plasma can thus occur. The possibility that NIL pools of beta-EI contribute to circulating levels of beta-EI is discussed. Removal of the AL depressed the beta-EI content of the hypothalamus and periventricular tissue at 3 and 20 weeks p.s. The Met-enkephalin-immunoreactivity (ME-I) content of the hypothalamus was, in contrast, unaffected. These animals still responded to stress at 20 weeks p.s. with a significant fall in hypothalamic levels of beta-EI. Extirpation of the NIL did not, in contrast, change brain levels of either beta-EI or ME-I. The presence of the AL, but not the NIL, is thus essential for the maintenance of usual levels of beta-EI and ME-I in the brain.

Animals↗

PubMed1982

Selective destruction of the ventral noradrenergic bundle but not of the locus coeruleus elevates plasma levels of beta-endorphin immunoreactivity in rats.

The present study examines the role of brain networks of noradrenaline (NA) in the control of pituitary secretion of beta-endorphin into systemic plasma. The blocker of NA synthesis, FLA-63, elicited a pronounced elevation in levels of beta-endorphin immunoreactivity (beta-EI) in systemic plasma and depleted the anterior but not the neurointermediate lobe content of beta-EI. This finding suggests the existence of a noradrenergic mechanism tonically inhibiting the secretion of adenohypophyseal pools of beta-EI into plasma. Selective destruction of the ventral noradrenergic bundle diminished the NA content of the hypothalamus but not the cortex, and produced an increase in plasma levels of beta-EI. Lesions of the locus coeruleus, the primary origin of the dorsal noradrenergic bundle, in contrast, decreased NA levels in the cortex but not the hypothalamus and failed to modify beta-EI levels in plasma. the ventral bundle may, thus, via a hypothalamic site of action, be the noradrenergic pathway inhibiting the secretion of beta-EI into the circulation.

Animals↗

PubMed1982

Evidence for an interrelationship between ventral noradrenergic bundle and CNS endorphins in the control of nociception in the rat.

The present paper examines the role of the ventral noradrenergic bundle (VB) in relation to endorphins in the control of nociception in the rat. Selective, bilateral destruction of the VB produced a substantial fall in hypothalamic levels of noradrenaline. On day 4 post-surgery, VB-lesioned rats displayed a pronounced elevation in basal nociceptive threshold. This proved to be reversible by the specific opioid antagonist, naloxone, evidential of its mediation by endorphins. It was, however, unaffected by dexamethasone, a suppressor of corticotrophic secretion of beta-endorphin, indicative that this pituitary pool of beta-endorphin was not responsible. On day 12, at which time the elevation in nociceptive threshold had disappeared, neither the time course nor the intensity of the antinociception elicited by acute stress or various doses of morphine was attenuated in VB-lesioned as compared to sham rats. These data are evidential that the VB may influence nociceptive thresholds via an interaction with a CNS endorphinergic network. They demonstrate, further, that the VB does not mediate a significant component of the antinociception generated by either morphine or stress.

Animals↗

PubMed1982

Lesions of the ventral noradrenergic (norepinephrinergic) bundle affect brain and pituitary pools of endorphins and the response of these to stress in rats.

The present study examines the interrelationship of the ventral noradrenergic (norepinephrinergic) bundle (VB) with brain and hypophyseal pools of endorphins. As compared to sham-operated rats, selective destruction of the VB depressed hypothalamic levels of norepinephrine and abolished the fall in these levels evoked by acute foot shock stress. Stress elevated plasma levels of beta-endorphin immunoreactivity (beta-EI) and both basal and poststress circulating levels of beta-EI were significantly greater in lesioned as compared to sham animals on days 4 and 10, but not 28, postsurgery. At each time, stress depleted the anterior and neurointermediate lobe content of beta-EI in both sham-operated and lesioned rats. These data indicate that stress mobilizes beta-EI from the pituitary into plasma and that the VB may inhibit the tonic and stress-elicited secretion of beta-EI into the circulation. In lesioned rats, a transient depression in basal levels of beta-EI in the septum and in those of met-enkephalin immunoreactivity (M-EI) in periventricular midbrain tissue was seen. Stress selectively depleted the beta-EI as compared to the M-EI content of discrete brain regions, including the septum and this periventricular tissue, in sham-operated animals. Lesioned rats also responded to stress with a fall in beta-EI levels and, in contrast to sham rats, with a decrease in the M-EI levels of the hypothalamus and periventricular tissue. These data demonstrate that the VB does not mediate the activation of brain beta-EI elicited by stress and suggest the existence of an interaction of the VB with certain brain pools of beta-EI and M-EI both tonically and under stress.

Animals↗

PubMedDate not supplied

Endogenous opioids, circadian rhythms, nutrient deprivation, eating and drinking.

Immunoreactive (ir) beta-endorphin (b-END) and dynorphin (DYN) in rat brain and pituitary were measured after food and water deprivation and from brains taken during either day or night. In other rats, eating and drinking were measured following lesions in the arcuate n. Ir-DYN levels are higher in hypothalamus and lower in pituitary at night. Deprivation, particularly water deprivation, increases hypothalamic, day-time ir-DYN. Water deprivation decreases pituitary levels of ir-DYN. Arcuate-lesions, depleting both ir-b-END and ir-DYN, do not modify total daily intake of water or food but does modify circadian rhythmicity of eating and drinking. These data support the conclusion that b-END and DYN are involved in maintaining day-night patterns of eating and drinking.

Animals↗

PubMedDate not supplied

Induction of audiogenic seizures in normal and genetically epilepsy-prone rats following focal microinjection of an excitant amino acid into reticular formation and auditory nuclei.

An excitant amino acid (EAA), N-methyl-D-aspartate (NMDA), induces susceptibility to seizures when bilaterally microinjected into subcortical auditory nuclei of normal rats. Thirty-five percent of animals exhibit only audiogenic seizures (AGS) after infusions of NMDA into inferior colliculus (IC). Infusions into cochlear nucleus and medial geniculate body never produce susceptibility to AGS without non-audiogenic seizures (N-AGS). The overall seizure incidence (AGS and N-AGS) with IC infusions is 100%, but the incidence is less than 50% with infusions into cochlear nucleus or medial geniculate body. Although AGS susceptibility is induced by NMDA infusions in normal animals, the seizures are submaximal in severity and lack tonic components. Bilateral infusions of NMDA into IC or reticular formation of the substrain of genetically epilepsy-prone rats (GEPRs) that exhibits submaximal AGS (GEPR-3s) do not increase seizure severity. These data along with studies showing increased EAA levels and excitotoxic-like damage in the IC of the GEPR and blockade of AGS with an EAA receptor antagonist or synthesis inhibitor suggest that an EAA in the IC is involved in initiation of AGS in the GEPR. However, EAA action in the GEPR IC is not sufficient to induce the complete spectrum of seizure behaviors, and additional mechanisms may be required for induction of maximal severity audiogenic seizures.

Acoustic Stimulation↗