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Biomedical subjects

M J Hosko

Publications and source records attributed to M J Hosko.

At least 19 recordsLinked to original sources
PubMed1986

Alteration of electrical correlates of sensory processing by tetrahydrocannabinol.

The action of tetrahydrocannabinol on the function of four multimodality responsive neocortical areas was assessed in the cat. Cats, anesthetized with alpha-chloralose, were subjected to auditory, somatosensory, and two types of visual stimulation. Simultaneous evoked field potentials and multiple-unit activity were recorded. The drug produced a significant reduction in evoked field responses at the three most rostral cortical areas, whereas responses at the posterior suprasylvian gyrus were spared. There were no significant differences between sensory modalities. In addition to being the first pharmacological study to demonstrate differential drug sensitivity between these polysensory areas, these studies localized an effect of tetrahydrocannabinol. Sensory evoked multiple-unit activity showed a pattern of change after THC consistent with a reduction in activity of pyramidal output cells and a concomitant increase in interneuron activity. The action of tetrahydrocannabinol on polysensory systems is important in attention and orientation.

Animals↗
PubMed1983

Differential effects of lysergic acid diethylamide, methysergide, and cyproheptadine on modality-specific and nonspecific sensory evoked potentials.

The effects of lysergic acid diethylamide (LSD), methysergide, and cyproheptadine on activity in classical primary pathways of the visual and somatosensory systems were compared with their effects on activity in sensory convergent (association) regions in alpha-chloralose-anesthetized cats. Those effects were blocked by cyproheptadine whereas methysergide potentiated the actions of LSD on visual primary activity. In contrast, LSD depressed the primary somatic pathway, at small doses (25 to 50 micrograms/kg) and facilitated the response at larger doses (200 micrograms/kg). Cyproheptadine and methysergide did not agonize these actions of LSD. The anterior marginal cortex, nucleus central median-parafascicularis, nucleus lateral posterior, and the superior colliculus, all sites of heterosensory convergence, were depressed by LSD. The depression of responses at heterosensory sites by LSD was blocked by cyproheptadine. Methysergide potentiated the LSD-induced depression of visual-evoked activity but not somatosensory activity. These results suggest that LSD depresses sensory activity in regions which integrate multiple sensory modalities independently of actions on sensory-specific pathways. These effects appear to involve a cyproheptadine-sensitive system.

Animals↗
PubMed1983

Voltage threshold and excitability among variously sized cat hindlimb motoneurons.

Intracellular recording has been performed to examine whether any differences in apparent initial-segment voltage threshold exist between types F and S cat triceps surae motoneurons. Voltage threshold was estimated using orthodromic action potentials initiated by large, monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by dorsal root stimulation. No significant differences in voltage threshold could be detected between types F and S motoneurons. Further, voltage thresholds did not covary with motoneuron input resistance, afterhyperpolarization duration, or the twitch contraction time of functionally isolated muscle units. Significant positive correlations were observed between voltage threshold and the motoneuron resting potential. Utilizing a compartmental neuron model, a theoretical analysis has been performed that examines the influence of specific passive membrane properties on current threshold for action potentials initiated by large, monosynaptic EPSPs. This analysis indicates that total membrane capacitance will be the primary determinant of these thresholds. Further analysis of available data suggests that active membrane properties will play a minimal role in setting these thresholds. Since specific membrane capacitance is likely to be similar among cat motoneurons, it is concluded that only size or surface area-related current threshold differences will exist among these cells for activation with brief currents such as those underlying large EPSPs. For motoneurons thus activated, it is suggested that variations in the excitatory/inhibitory balance or density of synaptic input would be the major mechanisms for producing differential recruitment thresholds among the motoneuron population. Other available evidence is discussed that indicates that factors intrinsic to the motoneurons themselves will contribute to the setting of functional recruitment thresholds for activation with longer duration currents.

Action Potentials↗
PubMed1982

Slowing of cortical somatosensory evoked activity by delta 9-tetrahydrocannabinol and dimethylheptylpyran in alpha-chloralose-anesthetized cats.

Somatosensory and visual evoked potentials in the classical afferent primary pathways in cats anesthetized with alpha-chloralose were studied in order to characterize the effects of delta 9-tetrahydrocannabinol (THC) and the synthetic analog, dimethylheptylpyran (DMHP) on central sensory processing. THC and DMHP slowed primary cortical responses to radial nerve or ventralis posterolateralis (VPL) stimulation in a dose dependent manner. THC did not alter VPL activity evoked by radial nerve stimulation. Amplitude of the primary somatic response was depressed at the 4 mg/kg dose. Responses of visual cortex and lateral geniculate nucleus, evoked by stimulation of optic chiasm, were unchanged at the doses studied. However, the nonmodality-specific response of the anterior marginal association cortex to stimulation of either modality was depressed by THC. Data suggest the association cortex which exhibits sensory convergence was most sensitive to the effects of THC. Findings were consistent with a thalamocortical site of action for THC. DMHP produced similar effects and was more potent.

Anesthesia↗
PubMed1981

Evidence for a caudal brainstem site of action for cannabinoid induced hypothermia.

delta 9-Tetrahydrocannabinol (THC), 11-hydroxy delta 9-tetrahydrocannabinol (11-OH-THC) and the synthetic dimethylheptyl analogue of THC (DMHP) were injected intracerebrally into proven chemosensitive sites in the hypothalamus of unanesthetized cats with implanted microinjection guide tubes. 100 micrograms of each compound was administered in a volume of 8 microliters. Chemosensitivity of all injection sites was established by microinjection of carbamylcholine to induce hyperthermia and tetrodotoxin to induce hypothermia. THC or its analogues produced no significant change in body temperature when injected intracerebrally. However, in the same animals, parenteral administration of THC, 11-OH-THC or DMHP (0.5 to 2.0 mg/kg) induced hypothermic responses ranging from -2.0 to -7.0 degrees C. Intravenous administration of THC was effective in blocking shivering induced by cooling the preoptic region in unanesthetized cats with implanted thermodes. In cats with mid-pontine transections, cooling of the spinal cord by perfusion with an epidural double wall cannula at temperatures of 30, 20, 10 and 0 degrees C produced graded shivering which was recorded electromyographically. Intravenous THC, (0.25-2.0 mg/kg) produced a dose-dependent attenuation of spinal cord induced shivering. These data plus results of prior studies suggest that the tetrahydrocannabinols produce their hypothermic effect at sites in the caudal brainstem. Suppression of shivering at the ponto medullary or spinal cord level may represent an important mechanism which contributes to the lowering of body temperature.

Animals↗
PubMed1980

Effect of delta 9-tetrahydrocannabinol on hypothalamic thermosensitive units.

Thermosensitive anterior hypothalamic neurons (pre-optic region) were studied in urethane and chloralose anesthetized cats in an attempt to characterize the hypothermic action of delta 9-THC at the neuronal level. One hundred and seventy-eight single neurons were isolated and subjected to thermal challenge, 66 were found to reproducibly alter firing frequency at a significant level (thermosensitivity (T.S.) greater than 0.75). Twenty-one of these units met the criteria for primary thermodetectors, 34 were heat-sensitive interneurons, and 11 were cold-sensitive interneurons. Administration of delta 9-THC (1.0-2.0 mg/kg i.v.) decreased the spontaneous firing and increased the T.S. of the primary thermodetector units. delta 9-THC also increased the spontaneous firing frequency as well as the T.S. of heat-sensitive interneurons, while decreasing both the T.S. and spontaneous firing of cold-sensitive interneurons. The decreased spontaneous firing of primary thermodetectors could result from altered facilitory or inhibitory influences converging on these cells. The increased thermosensitivity is consistent with the hypothesis that the pre-optic region modulates cannabinoid-induced hypothermia.

Animals↗
PubMed1977

Blockade of delta9-thc induced hypothermia in rats.

Pretreatment of rats with 6-hydroxydopamine over a narrow dose range (100 mg/kg i.p.), attenuated the hypothermic response elicited by administration of delta9-tetrahydrocannabinol (delta9-THC) (10 mg/kg i.p.). Pretreatment with hexamethonium (10 mg/kg i.p.) also attenuated the response. These findings suggest that the hypothermic response produced by delta9-THC administration in the rat is related to alteration of autonomic outflow.

Animals↗
PubMed1977

Effect of sojourn at 3200-m altitude on spinal reflexes in young adult males.

Studies of the H reflex and the Achilles tendon reflex (ATR) were performed in 12 healthy males under six conditions: 1) sea level control, 2) during the first 1-3 h at altitude while normoxic conditions were maintained, 3-5) at 6, 24 and 72 h of hypoxia, and 6) after Ve acclimatization at altitude in 5-14 d. After altitude acclimatization, the peak-to-peak amplitude of the H reflex and the ATR response was significantly elevated over control. A trend toward decreased amplitudes of both the ATR and the H reflex was observed at 6 h after the onset of hypoxia. There was no significant alteration in latency of the H reflex under any test condition. These findings suggest that sojourn at altitude by sea level residents induces changes in spinal motor reflexes. These changes are most probably mediated by altered high central modulation of the cord.

Acclimatization↗
PubMed1976

Hypothermia induced by delta9-tetrahydrocannabinol in rats with electrolytic lesions of preoptic region.

The preoptic region (POR) is a primary central site for thermoregulation. Bilateral lesions of POR disrupt thermoregulation, and in rats, produce a characteristic syndrome including hyperthermia. delta9-Tetrahydrocannabinol (delta9-THC), a potent hypothermic agent, appears to mediate this effect via some central mechanism. The studies reported here suggest that delta9-THC induces hypothermia at a site other than POR. Male Sprague-Dawley rats were divided into 2 groups, one with subsequently confirmed bilateral POR lesions and a sham operated group. The lesioned animals developed hyperthemia (+2.1degrees +/- 0.1degreesC, p less than 0.01) within 2 hr after surgery when compared to the sham operated controls. delta9-THC was administered intraperitoneally (5 and 10 mg/kg). Rectal temperature was recorded at 30 min intervals for 2.5 hr. Both lesioned and nonlesioned rats exhibited hypothermia within 30 min of delta9-THC administration. The hypothermic response to 5 and 10 mg/kg delta9-THC in the lesioned animals was significantly greater (p less than 0.05) and showed a trend toward longer duration than the hypothermia induced in the sham operated controls. These data demonstrate that delta9-THC is able to induce a hypothermic response in rats whose body temperatures were elevated by POR ablation. Although delta9-THC does not appear to act primarily at POR to induce hypothermia, it is evident than an intact POR plays a role in modifying the duration and magnitude of delta9-THC induced hypothermia.

Animals↗
PubMed1975

Effect of sojourn at 4,300 m altitude on electroencephalogram and visual evoked response.

The purpose of the present study was to determine the effect of sojourn at high altitude on cerebral electrical activity. Electroencephalographic (EEG) and visual evoked responses (VER) were recorded from seven healthy males under the following conditions: 1) during the first 2-3 h at 4,300 m altitude when Pao2 was maintained at 90 mmHg (control condition), 2) during the first 2-3 h of hypoxia (Pao2 = 40 mmHg), and 3) at 24- to 48-h intervals during the first 9-12 days of hypoxia. Electrode placement was according to the 10-20 International Electrode System. The VER was recorded from an electrode at the inion referred to the left ear. We found no significant changes from control cerebral electrical activity during the first 2-3 h of hypoxia. One subject's VER amplitude was greater than control on the 2nd and 3rd days of hypoxia and a similar change from control was consistently evident in a second subject beginning the 5th day of hypoxia. These changes suggest cortical depression. After the 5th day changes occurred in the remaining subjects which would be consistent with cortical excitation. In three subjects, EEG frequency was increased, amplitude decreased, and/or spiking became evident. In four subjects VER amplitude was reduced. Our findings provide support for the hypothesis that certain behavioral and physiological changes induced by sojourn at altitude could be caused by alterations in central nervous system function.

Acclimatization↗