Decrease In Spontaneous Activity Research Articles

Unit responses in the caudate nucleus to cumulative doses of morphine in unanesthetized, phenobarbital-treated rats

The effects of cumulative i.v. doses of morphine (1 to 30 mg/kg) on the spontaneous activity of single caudate nucleus neurons were evaluated in rats administered subsurgical doses of phenobarbital. At least 1 week prior to the experiment the animals were prepared with a chronic cranial implant which allowed subsequent restraint as well as the location and recording of neuronal activity with microelectrodes. The rats were pretreated with 40 or 140 mg/kg (i.p.) phenobarbital prior to each experiment. In both phenobarbital treatment groups, 50 to 61% of the neurons tested showed no specific morphine effect. The remainder of the neurons tested in each treatment group responded with morphine-specific increases or decreases in spontaneous activity. It is concluded that a lighter level of anesthesia permits a more dynamic range of caudate neuron responses to morphine.

Changes in noradrenergic terminal excitability induced by amphetamine and their relation to impulse traffic

The effects of amphetamine upon the terminal excitability of noradrenergic neurons of the nucleus locus coeruleus were studied in urethane anesthetized rats. Terminal excitability was measured by determining the stimulus currents necessary to evoke antidromic responses in locus coeruleus neurons from terminals in the frontal cortex. In most cases, terminal excitability was decreased following local infusion of amphetamine into the frontal cortex, while intravenous administration of the drug tended to increase terminal excitability. The decreased terminal excitability induced by local infusion of amphetamine appeared to be due to activation of alpha-adrenergic receptors located on the terminals of locus coeruleus neurons, since this effect mimics that of clonidine, a direct acting alpha-adrenergic agonist, and since the effect was abolished by pretreatment withalpha-methyl- p-tyrosine which disrupts the catecholamine liberating properties of amphetamine. Phentolamine, a direct acting alpha-adrenergic receptor antagonist was also found to block or reverse the effect of amphetamine. The changes in terminal excitability following intravenous injection of amphetamine appeared to be related to changes in the spontaneous activity of locus coeruleus neurons. A large decrease in spontaneous activity following intravenous administration of amphetamine was associated with increased terminal excitability, whereas when smaller changes in spontaneous activity occurred, terminal excitability was found to be decreased. These results are discussed with respect to the pharmacological properties of catecholaminergic neurons and the mechanisms of action of amphetamine.

Single cell activity in the noradrenergic A-5 region: Responses to drugs and peripheral manipulations of blood pressure

Single unit recordings were obtained from the region of the A-5 noradrenergic cell group in the ventrolateral tegmentum at the level of the exiting VIIth nerve. In this region a distinct cell population was identified which exhibited moderate spontaneous rates of activity, a regular firing pattern, wide action potentials, and a characteristic response to sensory stimulation consisting of a brief excitation followed by a more prolonged period of inhibition. Simultaneous visualization of recording sites and catecholamine cells by fluorescence histochemistry indicated a close association between the location of the recorded units and the A-5 noradrenergic cell group. Antidromic responses could be elicited by stimulation of the spinal cord and forebrain indicating that A-5 cells project both anteriorly and posteriorly. The spontaneous activity of A-5 cells was invariably suppressed by low doses of clonidine and l-amphetamine, while adjacent cells showed varying responses to these agents. The effects of clonidine and l-amphetamine could be reversed by low doses of the α 2-adrenoceptor antagonist, piperoxane. When applied by microiontophoresis, clonidine and norepinephrine were effective in inhibiting A-5 neurons. The rank order of inhibitory potencies for agonists applied microiontophoretically to A-5 neurons was characteristic of an α 2-receptor (i.e. clonidine > norepinephrine > phenylephrine). Thus, the physiological and pharmacological properties of the A-5 neurons closely matched those previously reported for noradrenergic neurons elsewhere. Sixty percent of A-5 neurons responded to peripherally induced changes in blood pressure with reciprocal changes in spontaneous firing rate. Increases in blood pressure led to decreases in spontaneous activity while decreases in pressure led to the opposite response. These observations are consistent with the proposed vasomotor role for the A-5 noradrenergic cell group.

Pacemaker currents in chick embryonic heart cells change with development.

The initial heartbeat of the chick embryo occurs shortly after the first day of incubation. The pacemaker of this beat originates in the region of the primitive heart destined to become sinoatrial tissue in the adult. Individual cells isolated from the atrial and ventricular portions of the embryonic heart are also capable of beating spontaneously at this stage. However, the intrinsic activity of these cells gradually diminishes from about day 7 until day 21 when the chick hatches. We have investigated these changes in automaticity by measuring membrane pacemaker currents with the voltage-clamp technique from aggregates of cells prepared from 7-, 12- and 17-day-old chick embryo cardiac ventricle. We report that there is a voltage and time dependent conductance at 7 days which is markedly reduced by 17 days. The reduction of this pacemaker current parallels the decrease of spontaneous activity in these preparations.

Starvation and the activities of glycolytic and gluconeogenic enzymes in skeletal muscles and liver of the plaice,Pleuronectes platessa

Changes in body index parameters and liver, red muscle and white muscle enzyme profiles have been determined in fed and four month starved plaice,Pleuronectes platessa. The results are compared to other vertebrates to estimate specific tissue metabolic patterns and changes in these patterns with starvation. 1. Liver demonstrates the lowest glycolytic but highest gluconeogenic capacity of the three tissues. Red muscle has little, if any, gluconeogenic potential, based upon low activities of phosphoenol pyruvate carboxykinase and glucose-6-phosphatase and no detectable activities of pyruvate carboxylase. Plaice white skeletal muscle has the highest glycolytic potential of the tissues studied. 2. Plaice starved for four months demonstrate significant reductions in liver-somatic index and red muscle-somatic index, and increases in tissue water contents (Table 1). Enzyme activities generally decline in both muscle types, but are maintained in the liver (Table 2). Activities of liver soluble phosphoenol pyruvate carboxykinase increase by approximately 8-fold, suggesting that the enzymic response to starvation in plaice is similar to that of mammals. 3. These results suggest that starvation in plaice is associated with both a decrease in spontaneous activity and metabolic capacity of skeletal muscles, and an enhanced potential for liver gluconeogenesis. Also, it is possible that the precursors for liver gluconeogenesis do not form pyruvate as an intermediate step.

Clinical Predictability of Intraventricular Hemorrhage in Preterm Infants

Ninety-eight infants of less than 35 weeks' gestation, consecutively admitted to a regional neonatal intensive care unit, were followed prior to computerized tomography (CT) scan for clinical signs of subependymal and/or intraventricular hemorrhage. The presence or absence of intracerebral hemorrhage was confirmed by CT scan in all patients, and the severity of hemorrhage was quantitated as mild, moderate, or marked. Thirty-seven out of 98 infants (38%) demonstrated intracerebral hemorrhage on CT scan; 20 of 37 (54%) were predicted clinically. Clinical predictability was related to severity of hemorrhage as quantitated by CT scan. Clinical signs that were found helpful in predicting subependymal and/or intraventricular hemorrhage were fall in hematocrit, failure of rise in hematocrit with transfusion of packed red blood cells, tight fontanel, decrease in spontaneous activity, decreased tone, abnormal eye signs, and seizures.

The bulbo-spinal indoleaminergic pathway in the frog

The role of the bulbo-spinal indoleaminergic pathway of the frog was investigated. Using the isolated spinal cord preparation, responses of motoneurons of segments 9 and 10 to lateral column stimulation were recorded from ventral roots (LC-VRP) and by intracellularly placed microelectrodes. Control responses were compared to those obtained after addition of substances known to alter indoleaminergic synthesis or receptor activation. Responses from spinal cords of animals that were pretreated with indoleamine-depleting agents were compared to mean control Procedures that inhibited indoleamine synthesis or blocked indoleamine receptors reduced motoneuronal activity. This was manifested as an increase in mean latency and a decrease in amplitude of the monosynaptic LC-VRP, an increased duration of suppression following an LC conditioning stimulus, and a decrease in spontaneous activity. In contrast to intracellularly recorded responses from control cords, those recorded under these conditions typically showed single spikes with longer latencies. Additions of indoleamine precursors to normal cords or to cords depleted of monoamines by reserpine shortened mean latencies, increased amplitudes of LC-elicited responses and caused an increase in spontaneous activity. These observations were recorded both extracellularly and intracellularly. Our results suggest that the bulbo-spinal indoleaminergic pathway modulates the output of motoneurons of the frog spinal cord.

Comparison of receptive-field properties of X and Y ganglion cells with X and Y lateral geniculate cells in the cat

1. To examine the transmission of visual information through the lateral geniculate nucleus, we have studied the receptive-field properties of 65 X and Y optic tract axons and compared them with the receptive-field properties of X and Y LGN cells in paralyzed cats anesthetized with N2O/O2 (70/30%). The same experimental conditions and quantitative methods have been used as in the preceding study of LGN cells (2). 2. The spatiotemporal organization of the receptive fields of X and Y retinal axons are similar to those of X and Y LGN cells. X ganglion cell receptive fields show a simple center-surround organization, whereas Y ganglion cell receptive fields show a more complex organization with three concentric regions: a central region of center-type response, a region of mixed center-type and surround-type responses, and a region of surround-type response. 3. The inhibitory strengh of the surrounding region was tested with a centrally located flashing light spot of successively increased diameter. As in the LGN, the inhibitory strenght of the surrounding region was stronger in retinal X-cells than in retinal Y-cells, and the strength of the inhibition decreased as the diameter of the receptive-field center increased. 4. The decrease of the inhibitory strength of the surrounding region with increasing distance from the receptive-field center was similar in the retina and in the LGN for cells belonging to the same class (X or Y) and having the same receptive-field center size. 5. The differences in properties in the LGN between small-field X-, large-field X-, and Y-cells are best explained by assuming that they are driven, respectively, by small-field X, large-field X, and Y retinal ganglion cells. There does not appear to be a significant mixing of properties either between cells having different receptive-field center sizes. 6. The principal transformation we found between retinal and LGN units is that X LGN cells have sharply lower spontaneous activities and driven activities, as compared with X ganglion cells. Y LGN units show only a small decrease in spontaneous activity in comparison with Y ganglion cells. 7. We conclude that there is a significant alteration in the LGN only in the properties of X-cells, possibly by way of a strong inhibitory pool converging on X LGN units. We further suggest that this inhibitory pool plays a role in the modulation of transmission of information through the LGN only in the X channel, while the Y channel appears to be relatively unaffected.

CHRONIC TOXICITY STUDY ON 4-ETHOXY-2-METHYL-5-MORPHOLINO-3(2H)-PYRIDAZINONE(M73101)IN RATS

Chronic toxicity and recovery tests of M73101, a new analgesic and antiinflammatory agent, were carried out using male and female JCL:SD rats. The drug was orally administered in doses of 0, 10, 30, 100, 300 and 1000mg/kg body weight/day for six months. A decrease of spontaneous activity in the group given 1000mg/kg and salivation in the groups given higher doses than 100mg/kg were observed during the administration period. In the 1000mg/kg group, inhibitions of body weight gain and of food efficiency were induced. An increased intake of water and a slight increase in urine volume and in urinary outputs of sodium, potassium and chloride were also observed in the highest dose group. No abnormality was observed in hematological findings in all groups tested. As to the biochemical findings of serum, the high dose groups showed an increase in total cholesterol, free cholesterol and triglyceride in females. Histopathological examination revealed a dose-dependent increase in liver weight and a hypertrophy of hepatocytes due to proliferation of smooth endplasmic reticulum. These changes were more intense in females than in males, suggesting the presence of a sex difference in the effect of M73101. A slight increase in kidney weight was also noted in the male groups given higher doses than 100mg/kg. A swelling and vacuolation of proximal tubular epithelial cells were observed in both sexes, and a single cell degeneration or necrosis was found electron-microscopically in the high dose groups. A change occuring in the gastro-intestinal tracts was ulcer formation due to swelling and subsequent desquemation of mucous epithelial cells. However the ulcer did not develop beyond lamina muscularis mucosae (grade I ulcer or erosion). In the recovery test, the symptoms and pathological changes mentioned above almost disappeared 4 to 8 weeks after the cessation of drug administration, except that a hypertrophy of hepatocytes still remained histologically to some extent in the highest dose groups. It was concluded that the target organs of M73101 were regarded virtually to be the liver, kidneys and gastro-intestinal tracts. The largest non-toxic dose of M73101 was considered to be about 30mg/kg body weight/day in male and female rats. Futhermore, it was suggested that the greatest safety dose was 100mg/kg body weight/day in male and female rats.

Chemosensitivity of hypophysiotropic neurons to the microelectrophoresis of biogenic amines

The purpose of this study was to determine whether norepinephrine (NE), dopamine (DA), serotonin (5-HT), acetylcholine (ACh) and glutamate (Glut) when applied in the immediate vicinity and in minute quantities to single neurons within the preoptic-hypothalamic complex via microelectrophoresis, could modulate their electrical activity. The action of these putative neurotransmitters on medial-preoptic (MPO) and arcuate-ventromedial (ARC-VM) neurons was studied in the urethane anesthetized, ovariectomized female rat. Multi-barrelled glass microelectrodes were used for extracellular recording and for microelectrophoresis of the putative transmitters. Four specific neuron types were identified by median eminence electrical stimulation; namely, antidromically identified (AI) MPO neurons, uninvaded MPO neurons, AI ARC-VM neurons and uninvaded ARC-VM neurons. The major findings based on responsive neurons (i.e., those neurons which reacted to the chemical application by an increase or decrease in spontaneous activity) are summarized. The data demonstrate that NE had a pronounced excitatory effect on uninvaded and AI ARC-VM neurons and an inhibitory influence on AI MPO neurons. The influence of dopamine was not as clearly defined, although there was a slight trend towards excitation in uninvaded MPO neurons and inhibition in AI MPO neurons. Results based on the testing with 5-HT showed it to have an inhibitory action on uninvaded MPO neurons. Furthermore, ACh and Glut were shown to have an excitatory action on the majority of responsive neurons tested. The remaining neurons tested with either NE, DA or 5-HT displayed a similar number of excitatory and inhibitory responses. The findings obtained provide positive support for a catecholaminergic and cholinergic regulation or neurons projecting towards the median eminence which are presumably involved in pituitary function.

Quantitative registration of motor disorders following bilateral lesions of substantia nigra in the rat.

Bilateral lesions in the substantia nigra were induced in rats trained in an instrumental learning program comparable with a fixed-interval schedule. General observations and examinations of rough motor behavior revealed rigidity, a decrease in spontaneous activity and a loss of postural reflexes. The analysis of lever-pressing rates results in a differentiation of rigidity and akinesia which is in accordance with the overt motor disturbances, dependent on the size of the nigral lesions.

Differential Response of Neurons of the Cochlear Nucleus to TTS-Producing Tones

The I/O functions of neurons in the chinchilla cochlear nucleus were measured before and after exposure to 8 min of a 95-dB-SPL tone at the characteristic frequency of the neurons. The exposure produced virtually no change in whole nerve AP but produced 14–19-dB shifts in auditory evoked response thresholds. “Flat primary” and “chopper” neurons showed a general decrease in spontaneous activity (SA), an 8–12-dB decrease in sensitivity, and no truncation of the neuron I/O function. “Pauser” and “primary” units showed little, if any, shift in sensitivity with relatively no change in SA. “On” neurons had higher SA after.exposure; their I/O function was depressed at low intensities and elevated at high intensities relative to the pre-exposure I/O. During the exposure, the activity of “on” neurons dropped below SA, while all other classes of neutrons showed marked increases in activity over the SA rate.

The effects of curare in Limulus central nervous system.

Exposure of Limulus abdominal ganglia to (+)-tubocurarine before or after cotton-mouth moccasin venom treatment resulted in a decrease of spontaneous activity in individual fibers in dorsal nerve roots and an inhibition of heart rate, but did not decrease responsiveness of the dorsal nerve to tactile stimulation. No effects of curare were obtained in nonsynaptic regions of nerve bundles either with or without venom pretreatment. Combining acetylcholine perfusion with (+)-tubocurarine resulted in a suppression of the stimulating effect of acetylcholine on dorsal nerve activity.

Effects of -methyl-p-tyrosine and L-DOPA on brain self-stimulation and motor activity in rats.

Rats with electrodes implanted in the posterior lateral hypothalamus and ventromedial tegmentum were trained to self-stimulate. Animals were treated (i.p.) first with alpha-methyl-p-tyrosine (alpha-MPT) and then L-DOPA; their self-stimulation rates and spontaneous behaviour were recorded. alpha-MPT (100 mg/kg) had an immediate and long lasting suppressive effect on self-stimulation, within the first half hour. L-DOPA administration failed to reinstate self-stimulation. Hypoactivity also followed alpha-MPT injections. While the behavioural changes were minimal after L-DOPA 50 mg/kg, a decrease of spontaneous activity and moderate hyper-reactivity were observed following L-DOPA at a dose of 200 mg/kg. Theoretical implications are discussed.

Some pharmacological effects of phenitrone and its interaction with Δ9-THC

We have investigated the pharmacological effects of phenitrone (3-(hexahydro-l-H-azepin-l-yl)-3′-nitropropiophenone HCl), a compound which has been reported to block and reverse the toxic and behavioral effects of hashish in dogs. There was no apparent blockade of cannabinoid-like activity when phenitrone was administered prior to or concomitantly with Δ 8-THC, Δ 9-THC, or the NIMH marihuana distillate in dogs and pigeons. However, phenitrone produced bizarre behavioral effects in dogs when given at a dose of 40 mg/kg and decreased the rate of conditioned key pecking for food at doses above 18 mg/kg in pigeons. When phenitrone and Δ 9-THC were given simultaneously, a dose-dependent inhibition of Δ 9-THC-induced activity in the mouse tail-flick test was observed. Phenitrone did not block hypothermia produced by either a single injection or 5 daily injections of Δ 9-THC in mice. Phenitrone also produced a decrease in spontaneous activity and had an LD 50 of 175 mg/kg i.p. in mice.

The effects of thyroxine and estradiol benzoate on wheel running activity in female rats

The administration of 30–50 μg thyroxine to female rats for 21 days disrupted wheel running activity and cyclic vaginal cornification. Thyroxine produced a decrease in spontaneous activity and the number of activity peaks, and resulted in prolonged vaginal cornification. Following ovariectomy, which reduced activity further, 15 μg/day estradiol benzoate increased overall activity. The data demonstrate that the activity changes produced by thyroxine administration are similar to those observed by others after thyroid removal. In addition, both procedures appear to produce their effects by altering ovarian functioning.

Effect of ACTH and hydrocortisone on multiple unit activity in the forebrain and thalamus in response to reticular stimulation

The spontaneous multiple unit activity (MUA) of various brain areas and their responsivity to mesencephalic reticular formation stimulation were studied in chronically implanted, freely moving, intact and adrenalectomized cats. Electrical stimulation of the mesencephalic reticular formation were performed exclusively during slow-wave sleep when the MUA was low and stable. Hydrocortisone resulted in a general decrease of MUA level in the mesencephalic reticular formation, the medial forebrain bundle at the anterior hypothalamic level, the medial preoptic area, the n. centromedianus and the fornix. The responsiveness of the structures to reticular stimulation was much lower in adrenalectomized than in normal animals and this reactivity was further lowered by hydrocortisone injection. ACTH injections resulted in a decrease of spontaneous activity and responsiveness in the medial preoptic area, both in normal and adrenalectomized animals, whereas a slight increase of MUA responsivity was found in the fornix and the medial forebrain bundle in response to reticular stimulation.

Increases in spontaneous activity following intermittent imipramine administration.

During this experiment subjects received 20 mg/kg of imipramine every third day until they had received a total of four injections. There was a decrease in spontaneous activity shortly after drug administration, but the drugged rats had activity levels which were significantly higher than those of subjects in a control group one day after injection.

Die wirkung von psychopharmaka auf visuell evozierte potentiale der katze

Были зapeгиcтpиpoвaны вызвaнныe cвeтoм пoтeнциaлы зpитeльнoй кopы y 25 кoшeк, a зaтeм иccлeдoвaны измeнeния этих пoтeнциaлoв пoд влияниeм хлopпpoмaзинa, бyтиpилпиpaзинa, хлopпpoтикceнa, хaлoпepидoлa, дeзипpaминa, aмитpиптилинa и диaзeпaмa. Лaтeнтныe пepиoды peaкций yдлинялиcь пo мepe yвeлихeния дoз этих aгeнтoв, on-peaкции в вызвaнных пoтeнциaлaх y бoльшинcтвa зивoтных были yвeлихeны. B нeкoтopых экcпepимeнтaх off-peaкции мoзнo былo видeть тoлькo пoд дeйcтвиeм фapмaкoлoгихecких вeщecтв; y бoльшинcтвa зивoтных off-peaкции yвeлихивaлиcь пo мepe yвeлихeния дoзы. зpитeльныe вызвaнныe пoтeнциaлы пoд влияниeм этих ядoв cтaнoвилиcь бoлee выpaзeнными. Эти эффeкты мoгyт быть интepпpeтиpoвaны кaк cлeдcтвиe yмeньшeния aктивиpyющeгo влияния дpyгих хacтeй мoзгa нa зpитeльнyю кopy и кaк cлeдcтвиe пoнизeния cпoнтaннoй aктивнocти в пepвихных aффepeнтных cиcтeмaх.