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Biomedical subjects

B L Jacobs

Publications and source records attributed to B L Jacobs.

At least 127 records · Page 7Linked to original sources
PubMed1984

Chloral hydrate anesthesia alters the responsiveness of central serotonergic neurons in the cat.

The influence of chloral hydrate anesthesia on the spontaneous activity and responsiveness of serotonergic neurons was examined by administering chloral hydrate (300 mg/kg, i.p.) to freely moving cats from which serotonergic unit activity in the dorsal raphe nucleus (DRN) was being recorded. Although chloral hydrate administration produced a surgical level of anesthesia within 15 min following injection, it produced only a small decrease (approximately 20%) in the spontaneous activity of DRN serotonergic neurons. In contrast, the responsiveness of these same neurons was greatly altered by chloral hydrate administration. By examining the same neuron before and after chloral hydrate injection, it was found that chloral hydrate anesthesia completely abolished the excitatory responses of DRN serotonergic neurons to auditory and visual stimuli, as well as their excitatory response to electrical stimulation of the gigantocellular tegmental field (FTG) in the pontine reticular formation. On the other hand, the inhibition of serotonergic neuron firing resulting from systemic administration of WB 4101 (1.0 mg/kg, i.p.), a selective alpha 1 adrenergic receptor antagonist, was greatly potentiated by chloral hydrate anesthesia. Therefore, these data indicate that chloral hydrate anesthesia produces profound changes in the physiological and pharmacological responses of central serotonergic neurons which are not predictable by examination of spontaneous activity alone. Furthermore, as discussed, it it not clear to what extent these confounding influences might generalize to other anesthetized or immobilized preparations. Thus, beyond the obvious advantage which allows for the study of relationships between neuronal activity and behavior, single unit studies conducted in awake, freely moving animals also may be of greater value for basic physiological and pharmacological studies.

Anesthesia, General↗
PubMed1984

Atlas of serotonergic cell bodies in the cat brainstem: an immunocytochemical analysis.

The localization and relative number of serotonergic (5HT) cell bodies in the brainstem of the cat were studied through the use of a specific immunocytochemical technique. A surprisingly large number of 5HT cells were found in regions in addition to the classical raphe nuclei (obscurus, pallidus, magnus, centralis superior, and dorsalis). Foremost among these were: the ventral medulla, just dorsal to the pyramidal tract and inferior olivary complex, and especially the area in and around the lateral reticular nucleus; the dorsal pons, surrounding the central reticular core, and in the central gray area; and a region in the mesencephalon, in and around the interpeduncular nucleus. The advantages and disadvantages of the existing schemas for subdividing and labeling groups of brain 5HT neurons are discussed.

Animals↗
PubMed1984

Activity of serotonin-containing neurons in nucleus centralis superior of freely moving cats.

Serotonergic neurons were recorded in the nucleus centralis superior (NCS) in freely moving cats and were initially identified on-line by their slow and regular spontaneous activity (mean 2.55 +/- 0.21 spikes/s). Discharge rates of NCS serotonergic neurons were highest during active waking (AW) (mean 2.94 +/- 0.28 spikes/s), decreased during slow-wave sleep (middle of SWS: mean 1.38 +/- 0.18 spikes/s), and were lowest during REM sleep (mean 0.46 +/- 0.13 spikes/s). The activity of serotonergic NCS neurons did not significantly increase during transient elevations of the EMG during AW but did significantly decrease immediately preceding, and during the occurrence of, SWS spindles. These neurons were responsive to phasic auditory and visual stimuli, with most neurons showing excitatory responses. In response to a small dose of the serotonin-specific agonist 5-methoxy-N,N-dimethyltryptamine (50 micrograms/kg, i.m.), NCS serotonergic neurons responded with a mean decrease in unit activity of 43.9 +/- 6.1%. Among the NCS serotonergic neurons a subpopulation differed from the remaining serotonergic neurons in that they showed a much smaller decrease in unit activity across the sleep-wake cycle and responded with an inhibition of activity to phasic auditory and visual stimuli. The results of this study are compared with those previously reported for serotonergic neurons in the dorsal raphe nucleus, nucleus raphe pallidus, and nucleus raphe magnus of freely moving cats.

Acoustic Stimulation↗
PubMed1983

Mechanism of interferon action. Effect of double-stranded RNA and the 5'-O-monophosphate form of 2',5'-oligoadenylate on the inhibition of reovirus mRNA translation in vitro.

The effect of reovirus double-stranded RNA (dsRNA) and 5'-O-monophosphate form of 2',5'-oligoadenylate (pA(2'p5'A)2) on the translation and degradation of reovirus messenger RNA and on protein phosphorylation was examined in extracts prepared from interferon-treated mouse L fibroblasts. The following results were obtained. 1) The enhanced degradation of reovirus [3H]mRNA observed in the presence of either dsRNA or the 5'-O-triphosphate form of 2',5'-oligoadenylate (pppA(2'p5'A)3) was completely blocked by pA(2'p5'A)2. 2) The dsRNA-dependent phosphorylation of protein P1 and the alpha subunit of eukaryotic initiation factor (eIF-2) depended in a similar manner upon the concentration of dsRNA and was optimal at low dsRNA concentrations (0.1 to 1 microgram/ml). However, high concentrations of dsRNA (greater than 100 micrograms/ml) drastically reduced the phosphorylation of both P1 and eIF-2 alpha. Neither P1 nor eIF-2 alpha phosphorylation was affected by either pA(2'p5'A)2 or pppA(2'p5'A)3. 3) The translation of reovirus mRNA in vitro was inhibited by the addition of either low concentrations of dsRNA or pppA(2'p5'A)3. Whereas pA(2'p5'A)2 completely reversed the pppA(2'p5'A)3-mediated inhibition of translation, the inhibition mediated by low concentrations of dsRNA was only partially reversed by pA(2'p5'A)2. Under conditions where the pppA-(2'p5'A)3mediated degradation of reovirus mRNA was blocked, the translation of reovirus mRNA was still inhibited by low but not by high concentrations of dsRNA in a manner that correlated with the activation of P1 and eIF-2 alpha phosphorylation. These results suggest that the pppA(2'p5'A)n-dependent ribonuclease is not required and that protein phosphorylation may indeed be sufficient for the dsRNA-dependent inhibition of reovirus mRNA translation in cell-free systems derived from interferon-treated mouse fibroblasts.

Adenine Nucleotides↗
PubMed1983

Raphe unit activity in freely moving cats is altered by manipulations of central but not peripheral motor systems.

Single unit activity of serotonergic neurons in the dorsal raphe nucleus of freely moving cats was recorded in experiments which manipulated central or peripheral motor systems. Unilateral microinjections of the cholinomimetic agent, carbachol, into the pontine tegmentum, produced muscle atonia. During these periods of drug-induced atonia, the activity of serotonergic neurons was reduced 97% below pre-drug baseline rates. In experiments where microinjections of carbachol did not produce muscle atonia, no significant change occurred in serotonergic unit discharge rate. Muscle tonus was also altered by systemic injections of mephenesin, a centrally acting muscle relaxant. A low dose of mephenesin (50 mg/kg) produced mild atonia which was correlated with a 16% reduction in serotonergic neuron discharge rate relative to pre-drug baseline. A higher dose of mephenesin (150 mg/kg) produced complete atonia, during which serotonergic unit activity was reduced by 68% below baseline firing rate. To distinguish between centrally and peripherally induced atonia, we injected either succinylcholine or dantrolene, systemically. These are both drugs whose muscle relaxant properties are known to be mediated by peripheral mechanisms. In neither case was a change in serotonergic unit discharge rate seen following drug-induced atonia. These data demonstrate that manipulation of central, but not peripheral, motor systems can profoundly affect the activity of serotonergic neurons of the dorsal raphe nucleus. Alternate hypotheses are also discussed.

Animals↗
PubMed1983

Response of dopaminergic neurons in cat to auditory stimuli presented across the sleep-waking cycle.

The response of dopaminergic neurons of the substantia nigra pars compacta to auditory clicks continuously presented across the sleep-wake cycle was studied in cats. The initial excitatory followed by inhibitory response to the click which occurred during quiet waking diminished as the cat progressed into slow-wave sleep and was absent during REM sleep. Upon awakening from REM sleep, dopamine neurons once again displayed an excitatory/inhibitory response to the clicks, implying that the decrease across the sleep-wake cycle was not attributable to long-term habituation.

Animals↗
PubMed1983

Raphe neurons: firing rate correlates with size of drug response.

Significant negative correlations were obtained between the spontaneous discharge rate during waking and the neural response to systemic injections of either 5-MeODMT or LSD for serotonergic neurons in the dorsal raphe nucleus, nucleus centralis superior, and nucleus raphe pallidus of unanesthetized and unrestrained cats. These data are discussed in terms of an hypothesis which accounts for both the rate of spontaneous activity of serotonergic neurons and the magnitude of their response to serotonin agonist drugs in terms of autoreceptor density on individual neurons.

Animals↗
PubMed1983

Raphe unit activity in freely moving cats: lack of diurnal variation.

Activity of presumed serotonin-containing neurons in the dorsal raphe nucleus of the cat was recorded across the sleep--waking cycle every 4 h, for 24 or 48 h. These neurons showed no diurnal variation in activity independent of behavioral state. This suggests that reports of diurnal fluctuations in serotonin metabolism are due either to differential patterns of sleep--wakefulness across the 24 h cycle and/or to a lack of tight coupling between neuronal activity and neurotransmitter metabolism.

Animals↗
PubMed1983

Dopaminergic unit activity in freely moving cats: lack of relationship to feeding, satiety, and glucose injections.

The activity of dopaminergic neurons in the substantia nigra was recorded from freely moving cats during feeding and satiety, and following injections of glucose. At no time during feeding or in the postprandial satiety period was there a significant increase or decrease in firing rate of these neurons relative to baseline. Additionally, no change in firing rate was observed following injections of glucose (300, 500 and 1000 mg/kg) or glucose in combination with insulin (300 mg/kg glucose and 0.8 units/kg insulin).

Animals↗
PubMed1983

Behavioral correlates of dopaminergic unit activity in freely moving cats.

Single unit activity of dopaminergic neurons in the substantia nigra was recorded in freely moving cats under a variety of conditions. These neurons displayed their highest discharge rate during active waking (3.68 +/- 0.30 spikes/s), which was 20% greater than their discharge rate during quiet waking (3.07 +/- 0.20). Although these cells fired somewhat faster during active waking, their activity displayed no correlation with phasic EMG changes, and, in general, their activity showed little relationship to overt behavioral changes. As the cat progressed from quiet waking through slow-wave sleep and REM sleep there was no significant change in either the rate or pattern of firing of dopaminergic neurons. In addition, no correlation was observed between the activity of these neurons and either sleep spindles or PGO waves. These neurons did respond, however, to the repeated presentation of a click or light flash with excitation followed by inhibition, with no evidence of habituation. One of the most impressive changes in dopaminergic unit activity was a large decrease in association with orienting responses. This was seen in over 50% of the cells in which this relationship was examined. As the behavioral orientation habituated with repeated stimulus presentation, so did the associated dopaminergic unit suppression. In conclusion, dopaminergic neurons maintain a remarkably constant rate and pattern of firing across a variety of behaviors and states. However, this stability can be dramatically altered under special circumstances, such as during and following orienting responses.

Animals↗
PubMed1982

Activity of serotonin-containing neurons in the nucleus raphe pallidus of freely moving cats.

Serotonergic neurons within nucleus raphe pallidus (NRP) of freely moving cats initially were distinguished by their slow (less than 8 Hz), regular discharge and long duration (mean = 2.3 ms) action potentials. The activity of serotonergic NRP neurons was highest during active waking (mean = 4.85 +/- 0.37 spikes/s) and gradually slowed, with little change in firing pattern, during the transition from waking through slow wave sleep (middle of SWS: mean = 3.76 +/- 0.36 spikes/s). In REM sleep there was a precipitous decrease in firing rate (mean = 0.92 +/- 0.23 spikes/s) and loss of discharge regularity. Although there was no significant difference in firing rate between active and quiet waking, discharge rates were significantly increased during transient elevations of the EMG, but these rate increases usually were associated with specific motor behaviors only. The activity of serotonergic NRP neurons during SWS was not related to the occurrence of either sleep spindles in the cortical EEG or PGO waves recorded from the lateral geniculate nucleus. These neurons also were relatively unresponsive to phasic auditory or visual stimuli, with most of the neurons examined showing weak excitatory responses. Activity of all serotonergic NRP neurons tested was suppressed (mean = -81.3 +/- 4.3%) by the serotonergic agonist 5-methoxy-N,N-dimethyltryptamine (250 micrograms/kg, i.m.). The results of this study are compared with those previously reported for serotonergic neurons in the dorsal raphe nucleus of freely moving cats and the issue of homogeneity in central serotonergic systems is discussed.

Acoustic Stimulation↗
PubMed1982

Medullary serotonergic neurons are insensitive to 5-MeoDMT and LSD.

A comparison was made of the effects of 5-MeoDMT or LSD on serotonergic unit activity in the dorsal raphe nucleus (DRN) and nucleus raphe pallidus (NRP) of freely moving cats. NRP neurons were substantially less responsive than DRN neurons to both drugs. NRP neurons were unresponsive to behaviorally effective low doses of these drugs whereas the activity of DRN neurons was strongly depressed. These data are discussed in terms of autoregulatory control of serotonergic neurons.

Animals↗
PubMed1982

Developmental analysis of raphe dorsalis unit activity in the rat.

Unit activity of raphe dorsalis neurons was recorded in rats between 3 and 24 days of age. Both a regular discharge pattern and a slow firing rate were observed as early as day 3. The frequency of discharge was not statistically different at any age from the mean discharge rate in the adult rat. It was concluded that the electrophysiological activity of 5-HT neurons develops early in the process of maturation, prior to that of the biochemistry and anatomy of these neurons.

Aging↗
PubMed1982

Behavioral effects of quipazine in the cat.

Administration of quipazine to cats elicits a number of behaviors, such as limb flicking abortive grooming, investigatory behavior and hallucinatory-like behavior, which we have previously proposed as an animal behavioral model for studying the actions of LSD and related hallucinogens. While recent studies have indicated that these model behaviors may not be totally specific for hallucinogenic drugs, the model can still be useful for studying drug action. Quipazine (0.5-5.0 mg/kg i.p.) produced significant increases in limb flicking, abortive grooming, investigatory behavior, hallucinatory-like behavior grooming, head and body shakes, staring and yawning. These behavioral changes persisted for 1-6 h, depending on the dose of quipazine employed. Administration of quipazine (5.0 mg/kg per day) for 5 consecutive days produced no significant tolerance effect on any of these model behaviors. These quipazine induced behavioral changes were potentiated by pretreatment with apomorphine, and partially blocked by pretreatment with haloperidol. Quipazine-induced behavioral changes were potentiated by prior serotonin depletion with p-chlorophenylalanine, and completely blocked by pretreatment with a monoamine oxidase inhibitor or the serotonin precursor, L-5-hydroxytryptophan. These quipazine-induced behavioral changes were also blocked by pretreatment with the serotonin receptor blockers, cinnanserin, methysergide or cyproheptadine. The mechanism of action of quipazine, as well as the neuropharmacology of the limb flick model, is discussed in the content of these studies with serotonergic and dopaminergic drugs.

Animals↗
PubMed1982

Raphe unit activity in freely moving cats: effects of phasic auditory and visual stimuli.

The effects of phasic auditory or visual stimuli upon the single unit activity of serotonergic neurons within the dorsal raphe nucleus (DRN) were studied in freely moving cats. The predominant response to auditory stimulation (86% of the cells) was excitation, with a mean latency of 40 +/- 3 ms (S.E.M.) and a mean duration of 64 +/- 4 ms. This was typically followed by a longer period (206 +/- 32 ms) with unit activity below the baseline level. This did not appear to be a stimulus-induced inhibition of unit activity, however, since its duration closely corresponded to the normal interspike interval for that particular neuron. The response to repetitive auditory stimulation showed no evidence of habituation and was even present during sleep. A similar response, although generally of lesser magnitude, was evoked by a phasic visual stimulation in 64% of the cells tested. The mean latency for the response to visual stimulation was 53 +/- 4 ms, the mean duration of excitation was 76 +/- 7 ms, and the mean duration of the subsequent suppressed period was 239 +/- 37 ms. The response to the visual stimulus also showed no evidence of habituation. These data indicate that serotonergic neurons of the DRN are driven, with similar temporal characteristics, by stimuli in two different sensory modalities. We hypothesize that these similar effects are attributable to a common excitatory input.

Acoustic Stimulation↗
PubMed1982

Assembly of vesicular stomatitis virus: distribution of the glycoprotein on the surface of infected cells.

This study demonstrates that the glycoprotein of vesicular stomatitis virus clusters in the plasma membrane of infected Chinese hamster lung cells during morphogenesis and suggests that viral nucleocapsids are required for this clustering. A mutant virus (ts E-1) which is temperature sensitive for the synthesis of viral nucleocapsids but not viral membrane proteins was used. The surface distribution of the viral glycoprotein in cells infected by this virus was determined by a specific indirect immunoferritin stain. Early in infection at permissive temperatures, the glycoprotein was randomly distributed on membrane ghosts. Later, clusters of ferritin the size and shape of virus particles were seen. In contrast, ghosts prepared from virus-infected cells maintained at a restrictive temperature always had a random distribution of viral glycoprotein.

Animals↗