Search PubMed⌕ Search

Biomedical subjects

M J Wayner

Publications and source records attributed to M J Wayner.

At least 55 records · Page 3Linked to original sources

The effects of purified Mojave toxin on rat synaptic membrane (Ca+2 + Mg+2)-ATPase and the dihydropyridine receptor.

Effects of purified Mojave toxin on rat synaptic membrane (Ca+2 + Mg+2)-ATPase and dihydropyridine receptor were determined. The toxin was observed to stimulate specifically (Ca+2 + Mg+2)-ATPase approximately two-fold with no effect on Mg+2 dependent ATPase activity. Examination of the effects of increasing amounts of purified Mojave toxin on binding of the calcium channel blocker, nitrendipine, indicated that the addition of 10 micrograms (4.5 X 10(-10) moles) of toxin resulted in greater than 90% inhibition of nitrendipine binding. Furthermore, binding studies revealed the toxin to have little affinity for the ligand indicating its interaction with calcium channel components. Since Mojave toxin has associated with it a phospholipase A2 activity, we investigated the effects of 4-bromophenacylbromide, a known inhibitor of phospholipase A2 activity in order to discern the possible effects of the purified toxin on synaptic membranes. At concentrations previously shown to be inhibitory of purified phospholipase A2 from cobra venom, both ATPase activity and nitrendipine binding of synaptic membranes were significantly inhibited. Thus we cannot rule out the possibility that the endogenous phospholipase activity of the purified toxin is responsible for its effects on the rat brain synaptic functions studied here. Binding studies conducted in the presence of verapamil and diltiazem indicated that the toxin interacts with allosteric sites responsible for regulation of the binding of nitrendipine. Although we have not tested the effects of Mojave toxin on other ion channels and/or receptors, results presented here suggest the potential usefulness of this toxin as a molecular probe of the calcium channel complex.

Animals↗

Direct effects of androgens on lateral hypothalamic neuronal activity in the male rat: I. A microiontophoretic study.

Unit neuronal activity in the lateral hypothalamic-medial forebrain bundle region (LHA-MFB) of the male rat is modified following an increase of plasma testosterone level. In order to determine possible direct action of hormones on LHA-MFB neurons, unit discharge frequencies were recorded during local microiontophoresis of testosterone and estradiol, and electroosmotic application of cholesterol. Thirteen cells did not respond, 9 were nonspecifically depressed by all the steroids tested, 13 were excited by both sex-steroids, and 11 were specifically activated by testosterone. The short latencies of the responses suggest a direct effect of steroids on the plasma membrane sites.

Action Potentials↗

Olfactory bulb neurons respond to gastric distension.

Single unit discharges in the olfactory bulb (OB) were recorded extracellularly in anesthetized rats during controlled gastric distension. The activity of 37 neurons in the periglomerular layer of the OB modulated by gastric distension was analyzed. Twelve of the 37 cells decreased, eight decreased and then increased in frequency, and 17 displayed more complex effects due to gastric distension. Generally, the latency of the responses to gastric distension was less than one second. All those cells which responded to gastric distension also responded to vagus nerve stimulation. This effect was abolished or attenuated by cutting the vagus nerve at the cervical level. The threshold volume by which the stomach was infused for the initial decrease in OB neuronal discharge frequency was 3.0 ml. When more than 8 ml were infused, increases in firing frequencies were always observed. The results of the present experiments indicate that the discharge frequency of the periglomerular OB neurons are modulated by visceral afferents.

Action Potentials↗

Effects of dopamine and norepinephrine on neuronal activity of the olfactory tubercle.

The effects of iontophoretic administration of norepinephrine (NE) and dopamine (DA) on olfactory tubercle (OT) neurons that respond to lateral hypothalamus (LH) or locus coeruleus (LC) electrical stimulation were studied. NE and DA decreased the frequency of OT neurons which were increased or decreased by the LH stimulation. An increased firing of OT neurons following NE or DA administration was less frequently observed. NE administration decreased the firing of OT neurons that responded to LC stimulation. These results suggest that the LC fibers which reach the OT use NE as a neurotransmitter. DA administration also suppressed the unitary discharge of OT neurons responding to LC stimulation. The increase in frequency of OT neurons observed following LH stimulation cannot be attributed to DA. The possibility that other suspected neural transmitters are involved in this effect is discussed.

Animals↗

Effects of neurotransmitters and vagus nerve stimulation on diencephalic and mesencephalic neuronal activity.

The effects of microiontophoretically applied neurotransmitters and cervical vagus nerve stimulation on neuronal discharge frequency was determined for cells located in the lateral hypothalamus-lateral preoptic area (LH-LPA), medial hypothalamus, thalamus-zona incerta area, and midbrain of anesthetized rats. Seven barrel electrodes were utilized to record simultaneously from and apply gamma aminobutyric acid (GABA), dopamine, glutamate, acetylcholine and norepinephrine to single neurons. Microiontophoretically applied GABA resulted in similar decreases in neuronal discharge frequency in all central areas tested. Thalamus-zona incerta cells were the most sensitive to GABA and required the lowest ejection current for threshold responses. Dopamine application resulted in increases and decreases in hypothalamic and mesencephalic neuronal discharge frequency. Thalamus-zona incerta neurons were the most sensitive to dopamine and exhibited only decreased activity during its application. Glutamate application resulted in a non-specific excitation of neurons. Acetylcholine induced increases and decreases in neuronal discharge frequency. Thalamus-zona incerta cells were the most sensitive to acetylcholine application. Hypothalamic neurons were the most sensitive to norepinephrine induced decreases in neuronal activity and effects in this area persisted for a prolonged period after norepinephrine was applied. Neuronal discharge frequency was significantly increased during vagus nerve stimulation in all central areas studied. Only hypothalamic neurons also exhibited decreased activity during vagus nerve stimulation. Results are discussed in terms of previous neurochemical and neurophysiological data and in terms of the importance of vagal afferents in the control of central neuronal activity.

Animals↗

Vagal and gastric connections to the central nervous system determined by the transport of horseradish peroxidase.

Horseradish peroxidase (HRP, Sigma Type VI) crystals were encased in a parafilm envelope and applied to the transected central ends of the left and right cervical vagus nerves and the anterior and posterior esophageal vagus nerves of adult male hooded rats. Injections of 30% HRP were made into the muscle wall of the fundus and antrum regions of the stomach. After 48 hr survival time, animals were perfused intracardially with a phosphate buffer plus sucrose wash followed by glutaraldehyde and paraformaldehyde fixative. The brain stem, spinal cord and corresponding dorsal root ganglia, superior cervical sympathetic ganglion, and the nodose ganglion were removed and cut into 50 micron sections. All tissue was processed with tetramethylbenzidine (TMB) for the blue reaction according to Mesulum and counterstained with neutral red. Sequential sections were examined under a microscope. Labeled neurons and nerve terminals were identified using bright and dark field condensers and polarized light. In tissue from animals that had HRP applied to the cervical vagus nerves, retrogradely labeled neurons were identified ipsilaterally in the medulla located in the dorsal motor nucleus of the vagus (DMN) and the nucleus ambiguus (NA). Labeled cells extended from the DMN into the spinal cord in ventral-medial and laminae X regions C1 and C2 of cervical segments. Many neurons were labeled in the nodose ganglion. Anterogradely labeled terminals were observed throughout and adjacent to the solitary nucleus (NTS) dorsal to the DMN and intermixed among labeled neurons located in the DMN. In tissue from animals that had HRP applied to the esophageal vagus nerves, similar labeling was observed. However, fewer neurons were identified in the NA, the nodose ganglion, and only in laminae X of the cervical spinal cord segments C1 and C2. Also, very little terminal labeling was observed in and adjacent to the NTS. Labeled neurons in tissue from animals that had HRP injected into the stomach wall were observed bilaterally in the DMN, nodose ganglion, and only in laminae X at the C1 and C2 levels of the spinal cord. Labeled neurons also were observed in the dorsal root ganglia of the thoracic cord. These data indicate that cervical cord and NA neurons are important in the supradiaphragmatic motor innervation by the vagus. Also, many afferents to the NTS originate above the diaphragm. In addition, some afferents from the stomach enter the central nervous system via the thoracic spinal cord.

Animals↗

Vagus nerve stimulation modifies the electrical activity of the olfactory bulb.

Evoked potential and unit activity recording techniques were used to study the effects of the vagus nerve stimulation on the olfactory bulb. A biphasic potential was evoked in the olfactory bulb by a single pulse delivered to the vagus nerve. Half of the neurons studied decreased discharge frequency after single pulse or train stimulation. The interval during which neurons ceased activity corresponded to the duration of the negative wave of the evoked potential. Responsive neurons were marked with horseradish peroxidase applied iontophoretically. Responsive neurons were located in the periglomerular layer of the olfactory bulb. These results suggest the existence of a vagus nerve-olfactory bulb pathway. The functional significance of this pathway is discussed.

Afferent Pathways↗

Limbic connections to the lateral preoptic area: a horseradish peroxidase study in the rat.

Horseradish peroxidase, 13% Sigma Type VI, was administered iontophoretically to the lateral preoptic area (LPA) of male hooded rats. Animals were perfused intracardially on the following day and brains were removed and sliced in the coronal plane into 50 microns sections. Alternate sections were processed with DAB and BDH for the brown and blue reaction products and later examined by bright and dark field microscopy for the presence and location of retrogradely labeled neurons. Results indicate that there are a significant number of limbic efferent connections to the LPA. Afferents to the LPA originate in the prefrontal corex, nucleus accumbens, diagonal band and olfactory structures, lateral and medial septum, stria hypothalamic tract and stria terminalis, the magnocellular and medial preoptic nuclei, along the extent of the medial forebrain bundle in the LPA and LH, anterior and basolateral amygdala, ventromedial caudate-putamen, stria medullaris and lateral habenula, the stellatocellular-periventricular, ventromedial, arcuate and anterior hypothalamic nuclei, the perifornical area, zona incerta, ventral medial thalamic area, ventral tegmental area of Tsai, interpeduncular nucleus, reticular zone of the substantia nigra, mesencephalic periaqueductal gray and reticular formation, all aspects of the raphe nuclei and the locus coeruleus. Results are discussed in terms of known anatomical and neurophysiological data and the similar limbic inputs observed for lateral hypothalamic neurons which are found along the extent of the medial forebrain bundle.

Animals↗

Increased urination following p-chloroamphetamine.

Para-chloramphetamine (PCA) is a drug whose long-term and short-term neurochemical and behavioral effects have received considerable attention. The purpose of the present study was to determine whether PCA produces acute urination, defecation, and body weight changes similar to that seen following various amphetamine derivatives. Following baseline test sessions, rats were administered either 0.5, 1.0, 2.0, 5.0 or 10.0 mg/kg of PCA or saline. Results indicated increased urination at some doses tested. Increased defecation, salivation, locomotor activities, and body weight losses were also observed. These data are discussed in terms of possible CNS or peripheral mechanisms of action.

Amphetamines↗

Effects of caffeine administration on food and water consumption under various experimental conditions.

The effects of caffeine on food and water intake was assessed in rats maintained under several experimental conditions. In Experiment 1, caffeine, 3.125, 6.25, 12.5, 25.0, 50.0 or 100.0 mg/kg was injected into 23 hr food deprived, 23 hr water deprived or ad lib animals. In Experiment 2, animals were adapted to a 21 hr food deprivation schedule and administered the same doses of caffeine as were used in Experiment 1. Results indicate that caffeine both enhances and decreases food and water intake and that the effects observed depend on the experimental circumstances.

Animals↗

Drugs and taste aversion.

The literature on the effects of drugs on the acquisition and the magnitude of taste aversion is reviewed and discussed. Then, the results of a series of experiments on the effects of phenobarbital and related drugs on taste aversion are reported. A standard taste aversion model was used in all experiments; test drugs were injected prior to drinking in a one bottle situation on the first test day following the taste aversion treatment. Phenobarbital in doses ranging from 20 to 80 mg/kg significantly attenuated taste aversion induced by lithium chloride (LiCl) and x-radiation, the maximal effect occurred with the 60 mg/kg dose. The attenuating effect was found to be dependent upon the magnitude of the aversion to the sapid solution. Phenobarbital completely abolished aversion produced by 0.375 mEq LiCl while the attenuation effect decreased linearly with higher doses of LiCl. Results also indicate that phenobarbital's attenuating effect cannot be solely attributed to its dipsogenic characteristic or to its state dependent learning effect. Attenuation of LiCl aversion to a saccharin solution was also observed following single doses of amobarbital, 30 mg/kg, pentobarbital, 15 mg/kg, and chloropromazine, 0.75 mg/kg. Taste aversion was not affected by other doses of those drugs or by hexobarbital, barbital, and chlordiazepoxide. Phenobarbital's attenuating effect on taste aversion is discussed in relation to other known behavioral and neurophysiological effects of the drug.

Animals↗

Mesencephalic reticular formation stimulation effects on hypothalamic neuronal activity.

The effects of mesencephalic reticular formation (RF) single pulse, 0.5 msec and 0-500 microA, stimulation on lateral preoptic-lateral hypothalamic (LPA-LH) neuronal activity were determined in anesthetized rats. In addition, the effects of LH stimulation on neural activity in the RF and periaqueductal gray (PAG) were evaluated. Recordings from 117 neurons indicate reciprocal connections between the LPA-LH and the mesencephalon. Stimulation of the RF affected 70% of the LPA-LH neurons tested. Short latency decreases in activity predominated indicating an inhibitory synaptic input from the RF to the LPA-LH. Short latency increases in discharge frequency were observed infrequently. Stimulation of the LH affected only 32% of the mesencephalic neurons tested. Short latency decreases in activity were usually observed indicating reciprocal inhibitory synaptic connections between the LPA-LH and the RF and periaqueductal gray. Antidromic responses verified these interconnections and revealed relatively slow conduction velocities of approximately 1.0 m/sec. Results are discussed in terms of the involvement of the LPA-LH and RF in sensorimotor functions, spinal motor excitability, and ingestive behavior.

Action Potentials↗

Effects of ventral tegmental area stimulation and microiontophoretic application of dopamine and norepinephrine on hypothalamic neurons.

The effects of ventral tegmental area of Tsai (VTA) stimulation on lateral hypothalamic (LH), lateral preoptic area (LPA). and medial hypothalamic neuronal activity were determined in anesthetized rats. Recordings from 81 hypothalamic neurons indicate that stimulation produces predominantly decreases in hypothalamic neuron activity. Increase in activity due to VTA stimulation occurred less frequently. Following single rectangular pulse stimulation, 0.5 msec. 0-500 microA, short latency decreases in activity occurred. Longer latency increases in discharge frequency were also observed. Dose response relations were established for 56% of the LH neurons, 78% of the LPA neurons, and for 82% of the medial hypothalamic neurons following VTA stimulation. Decreases and in a few cases increases in activity seemed to involve only one or two synapses. Antidromic responses verified interconnections between the VTA and the hypothalamus and revealed relatively slow conduction velocities of 0.45 and 0.81 m/sec. The changes in discharge frequency which occurred following VTA stimulation were similar in direction to the effects of the direct microiontophoretic application of dopamine (DA) or norepinephrine (NE). Since DA increased or decreased while NE decreased discharge frequency, these microiontophoretic tests indicated that the shorter latency VTA stimulation induced increases in decreases in neural activity were associated with VTA dopaminergic neuron stimulation and that in some cases short and long latency decreases in neuronal activity were due to activation of VTA ventral bundle NE fibers of passage or to indirect polysynaptic mechanisms. Results demonstrate the interconnections between various regions of the hypothalamus and the VTA along the extent of the medial forebrain bundle (MFB). The cross-validation of neuroanatomical and various electrophysiological methods in establishing the nature of hypothalamic connections was discussed.

Animals↗

Effects of periaqueductal gray stimulation of diencephalic neural activity.

The effects of ipsilateral mesencephalic periaqueductal gray (PAG) stimulation on lateral hypothalamic (LH), lateral preoptic area (LPA), and ventral and subthalamic activity were determined in anesthetized rats. Recordings from 119 diencephalic neurons indicate that the PAG provides a predominantly inhibitory input to diencephalic neurons. Excitatory input occurred infrequently in the hypothalamus and was not observed in the thalamus. Following single rectangular pulse stimulation, 0.5 msec, 0-500 micro A, short latency decreases in activity occurred. Longer latency increases in discharge frequency were also observed. Dose response relations were established for 74% of the LH neurons, 68% of the LPA neurons, and for 72% of the ventral and subthalamic neurons following VTA stimulation. Decreases and, in a few hypothalamic neurons, increases in activity seemed to involve only one or two synapses. The effects of contralateral PAG stimulation on LPA-LH neuronal activity were alos determined. Dose response relations were established for 66% of the LPA-LH neurons following contralateral stimulation. However, results were different in that many more cells were increased with a shorter latency and at a lower threshold following contralateral stimulation. Antidromic responses verified PAG and diencephalic interconnections and revealed relatively slow conduction velocities, less than 1.0 m/sec. Results were discussed in terms of the anatomy of known PAG pathways, PAG neuronal activation vs. PAG fibers of passage, and the functions of midbrain-hypothalamic interconnections in the integration of somatic, visceral and nociceptive sensory inputs.

Animals↗

Afferent connections to the lateral hypothalamus: a horseradish peroxidase study in the rat.

Horseradish peroxidase, 13% Sigma Type VI, was administered iontophoretically to the mid lateral hypothalamus (LH) of male hooded rats. Animals were perfused intracardially on the following day and brains were removed and sliced in the coronal or sagittal planes into 30-50 micrometer sections. Sections were processed with DAB and BDH for the brown and blue reaction products and later examined by bright and dark field microscopy for the presence and location of retrogradely labeled neurons. Results indicate that a significant number of afferent connections to the LH originate in the olfactory and accumbens nuclei, pyriform cortex, olfactory tracts, magnocellular and medial preoptic and anterior hypothalamic regions, stria terminalis, stria hypothalamic tract, diagonal tract of Broca, caudate-putamen and globus pallidus, internal capsule, lateral septal nuclei, lateral preoptic area and anterior medial forebrain bundle, the various amygdaloid nuclei, zona incerta, perifornical region, dorsal and ventral medial hypothalamic areas, supraoptic, paraventricular and periventricular nuclei, posterior hypothalamus and medial forebrain bundle, ventral thalamic nuclei, the fields of Forel, arcuate and mammillary nuclei, adjacent to the fasciculus retroflexus, in the ventral tegmental area of Tsai, interpeduncular nucleus, substantia nigra, mesencephalic reticular formation, periaqueductal gray, locus coeruleus and parabrachial region. Results are discussed in terms of previous anatomical and neurophysiological data, probable pathways, and the function of LH neurons.

Afferent Pathways↗

The effects of several barbiturates on lithium chloride induced taste aversion.

The effects of single doses of five barbiturates on LiCl induced saccharin aversion were examined. Twenty three hour fluid deprived rats were offered a novel 0.125% saccharin solution and then were injected with either 3.0 mEq/kg LiCl or 0.9% saline. On the first test day after conditioning the animals were injected with either 60 mg/kg sodium phenobarbital, 80 mg/kg sodium barbital, 30 mg/kg sodium amobarbital, 20 mg/kg sodium secobarbital, 9 mg/kg sodium pentobarbital or 0.9% saline, 15 min prior to the drinking session. Results indicate that only 9 mg/kg pentobarbital, 60 mg/kg phenobarbital, and 80 mg/kg barbital were effective in attenuating the LiCl induced saccharin aversion on the day of administration. In addition, dipsogenic effects for only 60 mg/kg phenobarbital and 30 mg/kg amobarbital were observed in the saline treated control groups. A synergistic interaction between the effects of LiCl and sodium phenobarbital, barbital, and secobarbital was also observed. Lithium chloride plus these barbiturates resulted in a longer term aversion to saccharin than LiCl alone and no barbiturate produced saccharin aversion when administered without LiCl.

Animals↗