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Biomedical subjects

R Emmers

Publications and source records attributed to R Emmers.

At least 19 recordsLinked to original sources
PubMed1989

Localization of serotonin receptors in the rat thalamus by electrophysiology and the action of 5-HTP-DP-hex.

This study was designed to pinpoint the site at which N-hexanoyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP-hex) exerts its previously reported effect on thalamic neurons in rats. The animals were prepared under chloralose-urethane anesthesia for a stereotaxic approach to either the nucleus ventralis posterolateralis (nVPL) or the centrum medianum-parafascicularis complex (CM-Pf) of the thalamus. Individual neurons in these nuclei were separately activated by single-pulse stimulation of the sciatic nerve or the thalamic fibers that form reciprocal connections between the CM-Pf and the second somatosensory (SII) region of the nVPL. Poststimulus time histograms were constructed from computer readouts of the stimulus-evoked responses of a neuron during a 500-ms period accumulated in a digital computer 100X. In addition, the number of spikes accumulated in each histogram was compared to the number of spikes accumulated under identical conditions on the same neuron after intracarotid infusion of 5-HTP-DP-hex. The effect of the drug was reversed by the infusion of 5-HTP. Statistical evaluation of the accumulated spike counts indicated that 5-HTP-DP-hex suppressed only the excitation of CM-Pf neurons from the SII of the nVPL; the input of the sciatic nerve into the CM-Pf remained unaltered. Furthermore, no effect was exerted by this dipeptide on the afferent excitation of neurons in the SII of the nVPL.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗
PubMed1987

Influence of a serotonin receptor antagonist, 5-HTP-DP-hex, on spinal and thalamic nociceptive neurons in rats.

The antinociceptive properties of a new synthetic dipeptide (N-hexanoyl-5-hydroxytryptophyl-5-hydroxytryptophan amide, or 5-HTP-DP-hex) were studied in rats by an electrophysiological method. After an i.p. injection of alpha-chloralose and urethane, the animals were prepared for stereotaxic approach to the nucleus ventralis posterolateralis of the thalamus. With tungsten microelectrodes, individual nociceptive neurons in the nucleus were identified by the sequence of spikes emitted in response to single-pulse stimulation of the sciatic nerve. In addition to the usual short-latency spikes, a nociceptive neuron fired late spikes at regular intervals within 500 ms following each stimulus. When the spikes were accumulated in poststimulus time histograms, the short-latency spikes compiled an intensity-related (I) peak. The late spikes formed modality-related (M) peaks with spacing characteristic of nociception. Intracarotid infusion of 5-HTP-DP-hex (1 mg/kg) elevated the delayed portion of the I peak and the first M peak. This effect was followed in 25 min by suppression of all M peaks. The control record could be reinstated at any time by 5-hydroxytryptophan (3.5 mg/kg), or by natural recovery in 2.5 h. Responses evoked from a thalamic nociceptive neuron by single-pulse stimulation of the spinothalamic tract were modified by 5-HTP-DP-hex in a similar manner, except that no elevation of the activity peaks was observed. As shown previously, elevation of the delayed I peak and M1 indicated an increased input of A-delta and C fibers, respectively. The increased input lowers the response threshold and may represent hyperalgesia. Suppression of the M peaks may result from altered function of the positive feedback loop in the nociceptive system at the thalamic level, and may represent analgesia. Naloxone, methysergide, as well as ketanserin had no significant effect on the response histograms. These findings suggested that 5-HTP-DP-hex, a known serotonin receptor antagonist, targeted its action on very specific receptors, and thus interfered with particular synaptic activity within the spinal cord and on the thalamic level.

5-Hydroxytryptophan↗
PubMed1985

Stimulation of the periaqueductal gray subdues sensitized pain in morphine- and meperidine-dependent rats.

Because increased tolerance of narcotics is marked by progressive deactivation of the descending antinociceptive system, a question was raised whether stimulation of the periaqueductal gray matter (PAG) would have any electroanalgetic effect in animals adapted to increasing doses of narcotics. The daily dose of morphine (10 mg/kg) administered to rats was increased on alternate days by 10 mg/kg to 100 mg/kg/day. To another group, the daily dose of meperidine was increased from 15 mg/kg by 15 mg/kg to 150 mg/kg/day. Electrophysiological experiments were conducted under chloralose and urethane anesthesia 16 h after the last injection of morphine or meperidine. Spike potentials evoked from individual neurons of the nucleus ventralis posterolateralis by single-pulse stimulation of the sciatic nerve were accumulated in poststimulus time histograms. For nociceptive neurons the histograms were characterized by a short-latency activity peak and at least two late (270 and 420 ms) peaks. For non-nociceptive neurons the histograms had no late activity peaks. In control rats, stimulation of the PAG (400 ms at 70/s) prior to each sciatic nerve pulse reorganized the late activity peaks of the nociceptive neurons: a single late peak occurred during the 280 to 400 ms poststimulus interval, indicating suppression of pain by electroanalgesia. In rats adapted to morphine or meperidine, intracarotid infusion of naloxone lowered the nociceptive threshold. Stimulation of the PAG reorganized the late peaks but only if the sciatic nerve stimulation was not increased. At the voltage used to stimulate the sciatic nerve in control animals, two separate late peaks appeared, which were subdued by PAG stimulation after intracarotid infusion of 5-hydroxytryptophan (5-HTP). These results affirmed previous findings that electroanalgesia is induced by activity in an ascending and a descending pathway, both originating from the PAG. Since the function of the descending pathway is impaired by repeated administration of narcotics, only the pathway ascending to the somesthetic thalamus can be activated to mask pain, unless 5-HTP is injected. The latter renews the functional capacity of the descending pathway and thus reinstates the full capacity of electroanalgesia.

Animals↗
PubMed1979

Interaction of neural systems which control nutritional balance.

The functional relationships of 5 nuclear masses of the cat brain were analyzed under conditions of general anesthesia by a combination of neurophysiological methods. The nuclear masses are known as (1) the area lateralis hypothalami (ALH), (2) the nucleus entopeduncularis (nEp), (3) the nucleus semilunaris accessorius (nSA), (4) the nucleus ventromedialis hypothalami (nVmH), and (5) the posterolateral portion of the zona incerta (ZI). Neurons of the ALH, nEp, and nVmH were tested for their responsiveness to electrical stimulation of the thalamic taste nucleus (nSA) and to intracarotid infusions of glucose and insulin. Following this, lesions were placed in some of the nuclei, and the responsiveness of the same neurons to glucose and insulin was re-evaluated. Additional experiments were performed to determine the influence of certain peripheral receptors on the 5 nuclear masses. Results indicated the following. (1) ALH-Ep neurons which are influenced by the nSA stimulation receive information about changes in plasma glucose from two sources: taste receptors and receptors located in the splanchnic area. The former are excited during the application of glucose to the tongue or with an increase in the plasma glucose concentration (intravascular taste); the latter, with a lowering of the plasma glucose level. (2) Destruction of the nSA leaves the ALH-Ep neurons unresponsive to glucose and insulin. (3) A negative feedback loop interrelates certain neurons of the ALH-Ep with the nVmH. (4) Interactions of the neurons of the 5 nuclear masses can account for the major events of the feeding cycle and for the specific hungers for some substances. Moreoever, the interactions can resolve several seemingly discordant experimental findings which have presented obstacles in previous attempts to link the control of nutrition with the availability of glucose to tissues.

Animals↗
PubMed1976

Thalamic mechanisms that process a temporal pulse code for pain.

The sequential ordering of spikes emitted by single thalamic neurons which respond to noxious stimulation was studied using rats anesthetized with a mixture of alpha-chloralose and urethane. An electrical stimulus applied to the sciatic nerve contralateral to the thalamic recording site fired single thalamic SII neurons with a short latency spike burst and with long latency spikes which occurred at relatively fixed intervals. On repetition of stimulation, the short latency spike burst formed a high amplitude peak on sequential spike density histograms (I of Fig. 2B); the long latency spikes formed peaks of relatively low amplitude (M1, M2, M3 of Fig. 2B). Histograms of touch and light pressure relay neurons found within the thalamic SII differed conspicuously from that of Fig. 2B. Further experiments revealed that the I peak contained frequency coded information about the stimulus intensity, whereas the M peaks with their temporal relationship to the I peak coded information pertaining to a particular sensory modality. The M peaks are formed by timed firing in a positive feedback loop found between the thalamic SII and the nucleus centrum medianum-nucleus parafascicularis (CM-Pf) neurons. Consequently, the M peaks can be abolished without losing the I peak by a lesion placed in a portion of the CM-Pf complex or by the administration or morphine which is able to disorganize the timing mechanism of the feedback loop. Therefore, it is reasonably certain that the modality coded by the M peaks is pain.

Action Potentials↗