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M H Roberts

Publications and source records attributed to M H Roberts.

At least 55 records · Page 3Linked to original sources
PubMed1989

Activation of cells in the anterior pretectal nucleus by dorsal column stimulation in the rat.

1. The responses of neurones in the anterior pretectal nucleus (APTN) to electrical stimulation of the dorsal columns at twice the threshold for A fibres were studied in the rat anaesthetized with urethane. 2. APTN cells were excited by dorsal column stimulation. Forty-six discharged phasically in response to a single stimulus. Sixteen cells did not respond phasically but slowly increased the discharge rate with repeated stimulation. 3. Electrical stimulation of the contralateral gracile fasciculus caused neurones in the APTN to discharge with a variable latency of 2-22 ms. Stimulations of the ipsilateral gracile and contralateral cuneate fasciculi had weaker effects. 4. Microinjection of DL-homocysteic acid into the contralateral gracile nucleus increased the discharge rate of APTN neurones. Microinjection of gamma-aminobutyric acid into the contralateral gracile nucleus blocked the gracile fasciculus evoked excitation of APTN neurones. 5. On thirteen occasions cells in the gracile nucleus were driven antidromically by electrical stimulation of the APTN. 6. It is concluded that electrical stimulation of the gracile fasciculus activates a monosynaptic excitatory input to the APTN.

Animals↗
PubMed1989

Antinociceptive effects of dorsal column stimulation in the rat: involvement of the anterior pretectal nucleus.

1. The effects of stimulating A fibres in the dorsal columns on the responses of dorsal horn neurones to intense cutaneous stimuli were studied in the rat anaesthetized with urethane. 2. Multireceptive cells deep in the lumbar dorsal horn were excited for 5-10 ms by dorsal column stimulation and subsequently responses to noxiously hot water placed on the cutaneous receptive field were reduced for the following 4-5 min. Seven of the cells studied projected to the brain via the contralateral anterolateral funiculus. 3. If the discharge of the multireceptive neurones was raised by ionophoretic application of DL-homocysteic acid, a brief period of inhibition lasting for 100-150 ms was seen following a single stimulus to the dorsal columns. Studies were conducted to determine if this brief inhibition could account for the long-lasting inhibition of responses to high-threshold stimuli. 4. Dorsal columns were transected at cervical levels. Stimulation caudal to the transection evoked only the brief excitation and subsequent inhibition for 100-150 ms. No long-lasting inhibition of high-threshold cutaneous afferent input was seen. 5. Stimulation of the dorsal columns rostral to transection did not evoke the brief excitation or inhibition of multireceptive dorsal horn neurones. However, the 4-5 min inhibition of responses to high-threshold cutaneous stimuli was present. 6. The long-lasting inhibition of responses to high-threshold stimuli by dorsal column stimulation was blocked by microinjection of gamma-aminobutyric acid into the anterior pretectal nucleus (APTN) but not by microinjections into adjacent areas of the brain. 7. Ipsilateral lesions of the dorsolateral funiculus at the cervical level also blocked the long-lasting inhibitory effects of dorsal column stimulation. 8. It is concluded that the brief excitation and inhibition of multireceptive dorsal horn neurones is due to antidromic action potentials passing caudally in the dorsal columns to activate spinal segmental mechanisms. The longer-lasting inhibition of responses to high-threshold cutaneous stimuli is due to action potentials ascending in the dorsal columns to activate cells in the APTN which in turn activate a descending inhibition mediated by the dorsolateral funiculus.

Animals↗
PubMed1989

Involvement of serotonin in nociceptive pathways.

New approaches in the design of analgesics emerged from the discovery that serotonin (5HT) is involved in the descending system (brain to spinal cord) that inhibits signals from peripheral nociceptors. However, the simple hypothesis that 5HT is a transmitter in this system requires elaboration, since not all agonists of 5HT are analgesics. In this commentary, the following questions are discussed: (a) do 5HT systems influence all responses to all types of noxious stimuli?, (b) is a 5HT synapse a necessary link in the analgesic system, (c) what is the location of the relevant 5HT receptor?, and (d) what is the relevant 5HT receptor subtype? The need for more adequate definition of the relevant 5HT receptor is stressed. Once this is achieved, a more rational approach to analgesic drug discovery will be provided by the design of selective agonists of this receptor.

Analgesics↗
PubMed1988

Evidence for excitatory 5-HT2-receptors on rat brainstem neurones.

1. The technique of microiontophoresis was used to investigate the identity of the receptor mediating the excitatory effects of 5-hydroxytryptamine (5-HT) upon neurones in the midline of the medullary brainstem of the rat in vivo. 2. The 5-HT1-like receptor agonists 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) failed to excite the majority of neurones excited by 5-HT. The mobilities of 5-CT and 8-OH-DPAT when tested in vitro were found not to differ significantly from that of 5-HT, suggesting that the lack of effect of these agonists was not due to a lower rate of release from the microelectrodes. 3. The excitatory responses to 5-HT were attenuated by the 5-HT 2-receptor antagonists ketanserin and methysergide when applied microiontophoretically or administered intravenously (0.3 and 1 mg kg-1 respectively). Excitatory responses to glutamate and noradrenaline were not reduced. 4. The 5-HT3-receptor antagonist MDL 72222 failed to attenuate selectively the excitatory response to 5-HT when applied either by microiontophoresis or administered intravenously (1 mg kg-1). 5. Microiontophoretic application of the alpha 1-adrenoceptor antagonist prazosin did not attenuate excitatory responses to either 5-HT or noradrenaline. Intravenously administered prazosin (0.8 mg kg-1) also failed to attenuate excitatory responses to 5-HT, but did block excitatory responses to noradrenaline. 6. These results suggest that 5-HT2-receptors, but not 5-HT1-like receptors, 5-HT3-receptors or alpha 1-adrenoceptors, are involved in the excitatory response of midline medullary neurones to 5-HT.

Action Potentials↗
PubMed1988

Evidence for depressant 5-HT1-like receptors on rat brainstem neurones.

1. The technique of microiontophoresis was used to evaluate the contribution of 5-HT1-like, 5-HT2- and 5-HT3-receptors to the depressant effects of 5-hydroxytryptamine (5-HT) on neurones in the midline of the medullary brainstem of the rat in vivo. 2. Depressant responses to 5-HT were resistant to antagonism by the 5-HT2-receptor antagonist ketanserin and the 5-HT3-receptor antagonist MDL 72222 applied either microiontophoretically or administered systemically. 3. Microiontophoretic or systemic administration of the 5-HT antagonist metergoline, which shows nanomolar affinity for the 5-HT1-binding site, also failed to attenuate the depressant responses to 5-HT. 4. Systemic administration of high doses of methysergide (30-40 mg kg-1) attenuated the depressant responses to 5-HT but did not block depressant responses to GABA or excitatory responses to glutamate. 5. The depressant effects of 5-HT were potently mimicked by the 5-HT1-like receptor agonists 5-carboxamidotryptamine and 8-OH-DPAT. 6. These results indicate that neither 5-HT2-receptors nor 5-HT3-receptors are involved in the depressant effects of 5-HT on midline brainstem neurones. The depressant effects of 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and blockade of the response to 5-HT by high doses of methysergide suggests the involvement of 5-HT1-like receptors. The lack of effect of metergoline, however, indicates that this receptor may be different from any of the 5-HT1 binding sites yet described.

Animals↗
PubMed1988

Effects of 5-hydroxytryptamine agonists and antagonists on the responses of rat spinal motoneurones to raphe obscurus stimulation.

1. The excitability of lumbar spinal motoneurones was studied in halothane-anaesthetized rats by recording with microelectrodes the amplitude of the population spike evoked antidromically by stimulation of the cut ventral roots. 2. Electrical stimulation of the nucleus raphe obscurus for 1 min at 20 Hz increased the population spike amplitude and, as shown by intracellular recording, depolarized motoneurones. This response could be mimicked by microinjection of DL-homocysteic acid into raphe obscurus but the response was not present in animals pretreated with the 5-hydroxytryptamine (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). 3. Microiontophoretically applied 5-HT had very similar effects on the extracellularly recorded population spike to those caused by stimulation of the raphe obscurus. These responses to 5-HT were larger in 5,7-DHT-pretreated animals. 4. The effects of 5-HT were potently mimicked by iontophoretically applied 5-carboxamidotryptamine but 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was without effect. 5. Antagonists were applied by microiontophoresis and also by intravenous injection. Ketanserin, the selective 5-HT2 antagonist, did not antagonize the effects of 5-HT. Neither did the 5-HT3-receptor antagonist MDL 72222 or the selective 5-HT1 binding ligand cyanopindolol. 6. The non-selective 5-HT1/5-HT2-receptor antagonist methysergide was an effective antagonist of both the effects of 5-HT and the response to raphe obscurus stimulation. Methysergide did not reduce the excitatory effects of noradrenaline. 7. It is concluded that 5-HT application and stimulation of raphe obscurus increase the excitability of motoneurones by an action on a 5-HT1-like receptor which appears to be different from the 5-HT1A-and the 5-HT1B-binding sites characterized by others.

Animals↗
PubMed1988

Effects of melatonin on 2-deoxy-[1-14C]glucose uptake within rat suprachiasmatic nucleus.

Previously, we have demonstrated that metabolic activity, shown by autoradiographic determination of 2-deoxy-[1-14C]glucose (2-DG) uptake, within the rat hypothalamic suprachiasmatic nuclei (SCN) was inhibited by subcutaneous injection of 1 mg/kg melatonin. To determine whether this effect was specific to a particular time of day, the effects of melatonin on 2-DG uptake were studied in several hypothalamic areas, including the SCN, supraoptic nuclei (SON), lateral hypothalamic area (LHA), and anterior hypothalamic area (AHA) every 4 h throughout the circadian day. In a second experiment, the effects of different melatonin doses were studied at the time of day at which melatonin had its maximal effect to determine the dose-response relationship of melatonin-induced inhibition of SCN 2-DG uptake. The data indicate that melatonin inhibited 2-DG uptake in the SCN alone at one time of day, primarily at circadian time (CT) 6 and CT10, 2-6 h before subjective dusk, and secondarily at CT22, just before subjective dawn. This effect was dose dependent with a 50% effective dose of 1.49 +/- 2.30 micrograms/kg. The temporal and dose-response characteristics of these effects are similar to those characterizing the entraining effects of melatonin on circadian patterns of locomotion and drinking.

Animals↗
PubMed1987

Melatonin inhibits metabolic activity in the rat suprachiasmatic nuclei.

The pineal hormone melatonin has been implicated in the regulation of circadian rhythms and in photoperiodic control of reproduction. The effects of melatonin require the hypothalamic suprachiasmatic nucleus (SCN), a principal pacemaker controlling circadian rhythms. To determine whether SCN activity was directly affected by exogenous melatonin, rats received either melatonin or saline injections 15 min before administration of 2-deoxy-[1-14C]glucose (2-DG) at two times of day, circadian time (CT) 10 and CT14, and the brains of these rats were processed for autoradiographic determination of 2-DG uptake within the SCN. We report that SCN 2-DG uptake was inhibited by melatonin at CT10, when 2-DG uptake is normally high, and unaffected at CT14, when 2-DG uptake is normally low. This indicates that the SCN may be neural substrates through which melatonin exerts at least some of its effects on mammalian physiology.

Animals↗
PubMed1987

Comparative studies of circadian pacemaker coupling in opisthobranch molluscs.

The eyes of several marine molluscs contain circadian pacemakers. The ocular pacemakers of one mollusc, Bulla gouldiana, are mutually coupled, and this coupling can be demonstrated in vitro. Induced phase separations between the two ocular pacemakers are reduced if the pacemakers are allowed to interact. The interaction between the pacemakers is mediated by the exchange of optic nerve impulses from eye to eye. In contrast, in vivo studies with another mollusc, Aplysia californica, have revealed that this snail's pacemakers are not strongly coupled. We have now determined in Bursatella leachi plei, an Opisthobranch closely related to A. californica, that the ocular pacemakers are mutually coupled. By virtue of the interaction between the pacemakers of B. leachi plei, the period of the ocular rhythm is increased by 1.5 h. In addition, eyes that remain attached to the nervous system show an increase in the sustainability of the free-running rhythm compared with isolated eyes. The increase in sustainability however, is due to the effects of attachment to the cerebral ganglion, and not the contralateral eye, since most single eyes attached to the brain show sustained, short-period rhythms. Thus, two properties of a circadian system, the pacemaker period and pacemaker sustainability, may be influenced by separate physiological mechanisms. We also confirm, using our in vitro techniques, the lack of strong coupling between the ocular pacemakers of A. californica.

Animals↗
PubMed1987

Localization of neuropeptides in efferent terminals of the eye in the marine snail, Bulla gouldiana.

Like several other opisthobranch molluscs, the marine snail Bulla gouldiana possesses two circadian pacemakers, one in each eye. The two ocular pacemakers are mutually coupled such that: the circadian rhythms of spontaneous electrical activity recorded from the optic nerve are normally synchronous and; if experimentally desynchronized the rhythms will return to the synchronized state. This coupling of the pacemakers is mediated by efferent fibers in the optic nerve, terminating in neuropil adjacent to the basal retinal neurons (BRNs), the putative circadian pacemaker cells. Attempts to identify neurotransmitters in efferent terminals that may be involved in the coupling process have failed. In the present study we demonstrate axons in the optic nerve and axon terminals adjacent to the BRNs that exhibit FMRF-amide- (molluscan cardioexcitatory peptide) and NPY-like (neuropeptide-Y) immunoreactivity. The pattern of immunoreactivity to both antisera is identical. Blocking studies indicate that both antisera are recognizing the same site, most likely the arginine-phenylalanine-amide terminus of FMRF, or an FMRF-like molecule. We conclude that FMRF is a candidate for the chemical mediator involved in the interaction between the two ocular pacemakers in Bulla gouldiana.

Animals↗
PubMed1987

Differentiation of the suprachiasmatic nucleus in fetal rat anterior hypothalamic transplants in oculo.

The capacity of the rat anterior hypothalamus, and particularly the suprachiasmatic nucleus (SCN), to develop and differentiate when removed from its normal environment was examined in this study using light and electron microscopy. The hypothalamus from fetuses ranging in age from embryonic day 12 (E 12) to E 16 was transplanted to the anterior chamber of the eye of adult rats. In initial experiments, we found that transplants from E 15 fetuses and older routinely differentiated into fields of neurons with extensive neuropil with an appearance similar to the anterior hypothalamic area. Groups of small, compactly organized neurons were observed only occasionally in this tissue. Ultrastructural analysis of these transplants typically revealed well-differentiated neuronal perikarya and neuropil with a complex synaptic organization similar in appearance to the normal rat anterior hypothalamic area. Occasionally both mature and immature tissue coexisted in some of the transplants. Tissue from young embryos (E 12-14) frequently showed development of a compact, small neuron nucleus with the cytoarchitectonic appearance of the SCN. At least 45 days were required after transplantation for the successful differentiation to occur in this situation. The SCN in these transplants displayed vasoactive intestinal polypeptide-immunoreactive cells and fibers surrounded by vasopressin-immunoreactive cells and fibers, similar to the pattern observed in the normal adult SCN. Our results indicate that the anterior hypothalamus will differentiate normally in oculo and that the phenotypic specification of the SCN occurs prior to the birthdate of its component neurons.

Animals↗
PubMed1987

Unavailability of polynuclear aromatic hydrocarbons from coal particles to the eastern oyster.

The accumulation by oysters of polycyclic aromatic hydrocarbons (PAH) from coal dust entering the estuarine environment has been postulated in the vicinity of coal transfer operations. Oysters Crassostrea virginica were exposed to coal dust plus 15 day leachate at concentrations of 10 mg litre(-1) and 1 mg litre(-1) coal dust for 28 days in a flow-through test system. Potential effects of the exposures were measured by comparing the uptake of PAH and the growth of the exposed animals versus control groups. Oysters sampled at 7, 14 and 28 days did not exhibit an increase in PAH body burden over control animals provided the guts were first purged of particulates. Even at the high test concentrations (10 mg litre(-1)), no effect of the exposure on shell growth was observed.

Journal Article↗
PubMed1987

The effects of intraperitoneal administration of antagonists and development of morphine tolerance on the antinociception induced by stimulating the anterior pretectal nucleus of the rat.

1 The effects of intraperitoneal administration of antagonists to morphine, 5-hydroxytryptamine (5-HT), noradrenaline and dopamine have been studied on the antinociceptive effects of electrical stimulation of the anterior pretectal nucleus (APtN) of the rat. 2 A 15 s period of 35 microA sine wave stimulation of APtN significantly increased the latency of the tail flick reflex to noxious heat for periods up to 1 h. 3 Naloxone (0.25-1.0 mg kg-1) attenuated the effects of APtN stimulation in a dose-dependent manner. In rats made tolerant to morphine by daily administration of morphine, the antinociceptive effects of APtN stimulation were significantly reduced. 4 The 5-HT receptor antagonists methysergide (5 mg kg-1) and ketanserin (1 mg kg-1), the dopamine receptor antagonist haloperidol (1 mg kg-1) and the beta-adrenoceptor antagonist propranolol (1 mg kg-1) had little effect on the antinociceptive effects of stimulating the APtN. 5 alpha-Adrenoceptor antagonists caused a dose-dependent antagonism of the response. The order of potency was; idazoxan greater than prazosin greater than phenoxybenzamine, the respective ED50 for each drug being 0.08: 0.45: 1.5 mg kg-1. 6 It is concluded that antagonism at opioid receptors and alpha-adrenoceptors but not beta-adrenoceptors, dopamine or 5-HT receptors reduces the antinociceptive effects of APtN stimulation. This differs from the reported effects of these antagonists on the antinociception caused by stimulating other sites in the brain.

Adrenergic alpha-Antagonists↗
PubMed1987

Anterior pretectal stimulation alters the responses of spinal dorsal horn neurones to cutaneous stimulation in the rat.

1. The behavioural effects of stimulating sites in the anterior pretectal nucleus (a.p.t.n.) were studied in unanaesthetized rats; 1-2 weeks later these rats were anaesthetized with Fluothane and the effects of similar electrical stimulation determined on the responses of spinal neurones to cutaneous stimuli. 2. Stimulation of the a.p.t.n. for 15 s with 35 microA r.m.s. sine-wave current inhibited the tail-flick response to noxious heat of unanaesthetized animals for up to 1 h. 3. Stimulation of the same sites in anaesthetized rats inhibited the responses to noxious heat of forty-two multireceptive and two high-threshold neurones located deep in the spinal dorsal horn. 4. The high-threshold responses of seven cells were unaffected or slightly potentiated by pretectal stimulation. These seven cells were all recorded from the dorsal margin of the dorsal horn, were not multireceptive neurones and could be made to discharge only by water above 50 degrees C. 5. The responses of twelve multireceptive cells to low-threshold stimulation were not affected by pretectal stimulation. All these cells were recorded from deep within the dorsal horn. 6. On ten occasions, cells deep in the dorsal horn were identified as projection neurones which were driven antidromically by high-frequency (300 Hz) stimulation of the contralateral anterolateral tract at cervical levels. The high-threshold responses of all these cells were reduced by pretectal stimulation. No cells were driven antidromically by pretectal stimulation. 7. Ipsilateral lesions of the dorsolateral funiculus abolished the inhibitory effects of prectectal stimulation. Lesions of the dorsal columns were without effect. 8. It is concluded that stimulation of the a.p.t.n. inhibits the tail-flick reflex of unanaesthetized rats and inhibits the high-threshold discharge of deep dorsal horn cells to cutaneous stimuli in anaesthetized rats. Cells recorded from the dorsal margin of the dorsal horn are not affected. The inhibition is mediated via the dorsolateral funiculus and affects cells which project rostrally in the contralateral anterolateral funiculus.

Action Potentials↗
PubMed1986

Brainstem mechanisms of antinociception. Effects of electrical stimulation and injection of morphine into the nucleus raphe magnus.

The microinjection of morphine into the nucleus raphe magnus (NRM) increased the tail-flick latency of rats but also increased the size of noxiously-evoked responses of dorsal horn neurones. Electrical stimulation of the raphe magnus reduced the response size of the same neurons to noxious stimulation. To control for the possibility that morphine had a membrane stabilising action upon cells in the raphe magnus, tetracaine was injected into the raphe magnus and found to reduce the size of noxiously-evoked responses of dorsal horn cells. Bilateral lesions of the dorsolateral funiculus reduced the effect on tail-flick latency of morphine injected into the raphe magnus, indicating that morphine was causing antinociception by an effect on descending systems. This effect of morphine was fundamentally different however from the effects of electrical stimulation. Antinociception may result from different mechanisms within the raphe magnus nucleus, affected by morphine and electrical stimulation.

Analgesia↗