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Biomedical subjects

M H Roberts

Publications and source records attributed to M H Roberts.

At least 73 records · Page 4Linked to original sources
PubMed1986

Microinjections of methyl-beta-carboline-3-carboxylate into the dorsal raphe nucleus: behavioural consequences.

Very small quantities (0.01-10 ng) of the inverse benzodiazepine receptor agonist, methyl-beta-carboline-3-carboxylate (beta-CCM) microinjected into the dorsal raphe nucleus (DRN) of the rat selectively reduced social interaction, an effect consistent with an increase in anxiety. Similarly, intraperitoneally injected beta-CCM, within a limited dose range, reduced social interaction without affecting locomotor activity. The benzodiazepine receptor antagonist, RO15-1788 (1 ng) microinjected into the DRN, reversed the suppression of social interaction induced by either intra-raphe or intraperitoneal beta-CCM. Histological examination of the beta-CCM microinjection sites showed that locations within the DRN were almost invariably associated with decreases in social interaction; microinjections failing to decrease social interaction were located primarily outside the DRN. We conclude that the DRN has a major role in expressing the anxiogenic effect of beta-CCM and it may therefore be an important area in the neuronal system controlling anxiety.

Animals↗
PubMed1986

Cellular analysis of ocular circadian pacemaker coupling in Bulla: role of efferent impulses in phase shifting.

The eyes of Bulla gouldiana, a marine snail, contain circadian oscillators that are coupled to each other. Obvious candidates for the coupling signals are the optic nerve compound action potentials (CAPs) that express the circadian rhythm and lead to efferent impulses in the contralateral optic nerve. In the present experiments, the role of the CAPs as coupling signals was evaluated. We found that, following desynchronization of the two ocular oscillators by phase-delaying one eye with manganese, subsequent phase shifts in the initially unshifted ocular rhythm only occurred during the time that efferent optic nerve signals were present. In addition, in the absence of ocular desynchrony, phase shifts of the ocular rhythm could still be effected by activation of the efferent pathway. The influence of efferent impulses on identified retinal cells was also evaluated. No effect of efferent signals on receptor layer cells was detected, while it was found that efferent impulses generated depolarizations in basal retinal neurons (BRNs), the putative circadian oscillator cells. Depolarization of the BRNs has been shown previously to be involved in the light entrainment pathway. Depolarization appears to be similarly involved in the coupling pathway, since membrane depolarizations that mimicked the efferent-induced postsynaptic potentials likewise generated phase shifts of the ocular rhythm.

Action Potentials↗
PubMed1985

An assessment of the antinociceptive and aversive effects of stimulating identified sites in the rat brain.

At many sites in the brain electrical stimulation with low current intensity is both aversive and causes antinociception. In view of the well documented antinociception caused by various types of stress and pain it is possible that in some parts of the brain the antinociception is secondary to the stress of the stimulation. At 114 sites in the rat brain the intensity of stimulation required to evoke an aversive response has been compared with the antinociceptive current intensity. Only stimulation in the dorsal hippocampus and pretectal area caused antinociception without significant aversion. Strong aversion resulted from stimulation of 46% of the sites including the central gray and nucleus raphe magnus. Antinociception was significantly correlated with the aversiveness of the stimulation although in 15% of the stimulation sites strong aversion was seen with no antinociception. It is concluded that there can be little justification in assigning a primary antinociceptive role to a brain area which evokes strong escape reactions when stimulated.

Animals↗
PubMed1985

The effects of methyl beta-carboline-3-carboxylate on social interaction and locomotor activity when microinjected into the nucleus raphé dorsalis of the rat.

Intraperitoneal and intracerebral injections of methyl beta-carboline-3-carboxylate (beta CCM) and intracerebral injections of RO 15-1788 were given to rats. The performance of the rats in the social interaction test was measured to determine if changes in social interaction induced by beta CCM were mediated in part by the nucleus raphé dorsalis (NRD). Intraperitoneal injections of beta CCM, 2 and 4 mg kg-1, reduced social interaction. Intracerebral microinjections of beta CCM (10-0.1 ng in 0.5 microliter) into the NRD reduced social interaction. Injections outside the NRD did not have this effect. Intracerebral microinjections of RO 15-1788 (1 ng in 0.5 microliters) into the NRD had no effect when given alone, but blocked the reduction in social interaction caused by intracerebral or intraperitoneal injections of beta CCM. No effect was observed when R 15-1788 was microinjected into sites outside the NRD. Changes in social interaction may reflect changes in anxiety. The NRD may be one of the important sites for the expression of the anxiogenic actions of beta CCM.

Animals↗
PubMed1985

Analysis of mutual circadian pacemaker coupling between the two eyes of Bulla.

The eyes of Bulla, a marine snail, express a circadian rhythm in the frequency of optic nerve compound action potentials (CAPs). The two ocular pacemakers are mutually coupled, and their interaction can be observed in vitro. The evidence for mutual coupling, as demonstrated in the present experiments, was as follows: (1) When intact Bulla were placed into darkness for up to 72 days, the two pacemakers did not desynchronize. (2) The free-running period of the ocular rhythm in the intact system (24.4 hr) was longer than the free-running period of the rhythm recorded from isolated eyes (23.7 hr). (3) When the two ocular pacemakers were experimentally desynchronized in vitro, resynchronization occurred if the pacemakers were allowed to interact for 48 hr. The coupling signals are most likely the CAPs. These impulses are conducted through the central ganglia and emerge as efferent impulses in the opposite optic nerve. Ocular-derived efferent impulse activity affects spontaneous impulse production in the target eye and alters the waveform of the circadian rhythm. The coupling pathway mediating syncrhonization consists of the two optic nerves, the cerebral ganglia, and the cerebral commissure. The demonstration of coupling in vitro provides a new opportunity for studying the cellular mechanisms underlying mutual pacemaker entrainment.

Action Potentials↗
PubMed1984

The effect of modification of 5-hydroxytryptamine function in nucleus raphe magnus on nociceptive threshold.

Thresholds to noxious heat stimulation were increased following microinjection of zimelidine, an inhibitor of 5-hydroxytryptamine (5-HT) re-uptake, into the nucleus raphe magnus (NRM) of rats. Pretreatment with intraperitoneally given cinanserin reduced this effect but pretreatment with intraperitoneally given phenoxybenzamine did not. Fenfluramine, which causes the release of 5-HT from synaptic terminals also elevated nociceptive thresholds following microinjection into NRM. Subanalgesic doses of morphine or zimelidine elevated nociceptive thresholds when microinjected together into NRM. The elevation of nociceptive threshold produced by microinjection of morphine into NRM was reduced by simultaneous microinjection of cinanserin into NRM. Cinanserin alone had no effect when microinjected into NRM. These findings suggest that inhibition of the re-uptake of 5-HT in NRM can elevate nociceptive thresholds and that there may be an interaction between the effects of morphine and 5-HT in NRM.

Animals↗
PubMed1984

5-Hydroxytryptamine and antinociception.

The considerable evidence supporting a role for 5-hydroxytryptamine (5-HT) in the modulation of nociceptive thresholds is reviewed. The postulate that an antinociceptive system of neurones projects from periaqueductal gray (PAG) to nucleus raphe magnus (NRM) and then to the dorsal horn, via cells containing 5-HT, has proved difficult to support experimentally. 5-Hydroxytryptamine, applied iontophoretically to dorsal horn neurones, does reduce the nociceptive responses of these neurones but it is not clear that activity in 5-HT cells of the raphe-spinal system is responsible for the descending inhibition of nociception. Although antagonists of 5-HT block some of the antinociceptive effects of both stimulation of the periaqueductal gray and systemically-applied morphine, they do not block the centrifugal inhibition of dorsal horn cells or the effects of iontophoretically applied 5-HT. Nor do they displace [3H]5-HT binding at low concentrations. Damage to, or selective depletion of 5-HT from the raphe-spinal 5-HT system has been reported not to alter nociceptive thresholds or the effects of stimulation of the periaqueductal gray. There is anatomical evidence for cells in the periaqueductal gray which contain 5-HT and project to the n. raphe magnus. Microinjected into the n. raphe magnus, 5-HT is antinociceptive in the tail-flick test and microinjection of an inhibitor of uptake of 5-HT or a 5-HT releasing agent, both cause antinociception. Furthermore, the effects of electrical stimulation of the periaqueductal gray are blocked by microinjection of a 5-HT antagonist into the n. raphe magnus.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1984

Antinociception from a stereospecific action of morphine microinjected into the brainstem: a local or distant site of action?

Morphine (1 microgram) was microinjected into rats in the midline medullary nucleus raphe magnus (NRM); 1 mm lateral into nucleus reticularis paragigantocellularis (NRPG); 2 mm lateral into the VIIth nerve nucleus and 3 mm lateral into the Vth nerve nucleus. The time course of changes in the sensitivity to noxious heat was followed by the tail flick test. Significant and prolonged antinociception was seen following microinjection into NRPG. At sites 1 mm from NRPG very weak effects were seen and at 2 mm from NRPG no antinociception occurred. It is concluded that 1 microgram of morphine microinjected into the brainstem is unlikely to cause antinociception by entering the circulation and having effects at remote sites. The distance diffused by morphine to cause significant antinociception after microinjection of 1 microgram is less than 1 mm. Levorphanol (1 microgram) had very similar effects to morphine but dextrorphan and saline were ineffective. It is concluded that although the concentrations achieved following microinjections may be high, they are not excessive as the effects show stereospecificity. The concentrations of endogenous substances released into the synaptic cleft may also be high.

Analgesics↗
PubMed1983

Methyl-beta-carboline-3-carboxylate attenuates GABA effects in rat brain hippocampus in vivo.

The benzodiazepine receptor ligand methyl-beta-carboline-3-carboxylate was applied by micropressure-ejection in the course of extracellular recordings of spontaneously firing rat brain hippocampal pyramidal cells in vivo. Methyl-beta-carboline-3-carboxylate was found to attenuate the depressant effects of GABA, increase the spontaneous firing rate and increase the tendency to fire in bursts. The possibility that both firing rate and burst firing in the hippocampus are controlled by the inhibitory neurotransmitter GABA is discussed. Methyl-beta-carboline-3-carboxylate is a convulsant and this action on GABA could explain the mechanism. Methyl-beta-carboline-3-carboxylate seems to have effects on the firing of CA1 neurons which are similar to the effects reported for ethyl-beta-carboline-3-carboxylate and opposite to those reported for the benzodiazepines midazolam and diazepam.

Animals↗
PubMed1983

Mutual coupling between the ocular circadian pacemakers of Bulla gouldiana.

The ocular circadian pacemakers of Bulla gouldiana were found to be mutually coupled, and their interaction could be observed in an isolated nervous system maintained in vitro. Experimentally induced phase separations between the two ocular pacemakers were reduced when the eyes were allowed to interact for 48 hours. The reduction in phase separation did not occur however when the cerebral commissure was severed, indicating that this neural tract is a critical pathway coupling these two circadian clocks.

Animals↗
PubMed1983

Hyperalgesia and the reduction of monoamines resulting from lesions of the dorsolateral funiculus.

Unilateral lesions of the dorsolateral funiculus (DLF) in the rat resulted in unilateral hyperalgesia as revealed by a hindpaw withdrawal test to heat. Larger lesions involving the dorsal column and ventrolateral quadrant did not cause hyperalgesia. The levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA) and dopamine (DA) were measured in the lumbar dorsal quadrant using high performance liquid chromatography (HPLC). In hyperalgesic animals DLF lesions caused an ipsilateral reduction of all the amines and a contralateral reduction of 5-HT and NA. This suggests that serotonergic and noradrenergic axons in the DLF give a contralateral innervation. A correlation was sought between the reduction of amine level and the degree of hyperalgesia shown by individual rats on lesioned and unlesioned sides of the cord. No consistent correlation was found with any of the amines.

Animals↗
PubMed1983

Confirmation of a de novo duplication, dup(10)(q24 leads to q26), by GOT1 gene dosage studies.

A girl with mental retardation and the facies associated with the distal 10q duplication syndrome was found to have a tandem duplication of 10q24 to 10q26. This was confirmed by gene dosage studies of glutamic oxaloacetic transaminase 1. The clinical features of this patient are compared with those of other reported cases of the distal 10q duplication syndrome with duplication-deficiency karyotypes due to familial reciprocal translocations or inversions or with tandem duplication of a more proximal region of 10q. Reports of tandem duplications in man and possible mechanisms of origin are discussed.

Aspartate Aminotransferases↗
PubMed1982

Two children with deletion of the long arm of chromosome 4 with breakpoint at band q33.

A 10-year-old boy with developmental delay, craniofacial dysmorphia, malformations of the hands and feet and a cardiac malformation was found to have a small deletion of the distal region (q33 leads to qter) of the long arm of a chromosome 4. The clinical findings in this case are compared with those of a 17-week-old girl recently found to have the same deletion. Two additional patients with similar small deletions have been described in the literature. The similarity among the cases suggests the possibility of a deletion (4) (q33) syndrome. The major features of the syndrome are similar to those of larger deletions of the long arm of chromosome 4 and include mental and growth retardation, craniofacial dysmorphia including upslanting palpebral fissures, depressed nasal bridge, anteverted nares, abnormally shaped ears and micrognathia, and cardiac defects.

Abnormalities, Multiple↗
PubMed1981

5-Hydroxytryptamine reduces substance P responses on dorsal horn interneurones: a possible interaction of neurotransmitters.

Responses of dorsal horn neurons to iontophoretically administered substance P were attenuated by iontophoretically applied 5-hydroxytryptamine (5-HT). This occurred even when 5-HT alone had no effect on the excitability of the cell. 5-HT did not attenuate responses to iontophoretic application of glutamate. It has been suggested that 5-HT presynaptically inhibits the nociceptive afferents but direct application of 5-HT whilst recording the polarisation of primary afferents in vivo failed to confirm this postulate. These results cannot be explained by a presynaptic inhibition of primary afferents by 5-HT and it is suggested that 5-HT is either acting directly on the substance P receptor or on the receptor-excitation coupling mechanism.

Afferent Pathways↗