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Biomedical subjects

M J Wayner

Publications and source records attributed to M J Wayner.

At least 145 records · Page 8Linked to original sources

Effects of ethyl alcohol on central neurons.-.

A method was developed for the electrophoretic application of ethyl alcohol through one capillary in a multibarrel microelectrode array in the vicinity of the recording electode. Effects of ethyl alcohol and angiotensin II applied by means of electrophoretic ejection and ethanol administered intravenously on the frequency of extracellularly recorded action potentials of brain cells were determined. A total of 87 neurons in four different parts of the brain in female hooded rats anesthetized with a mixture of urethan and chloralose were tested. Results reveal that a most sensitive neurons appear to be those of the lateral hypothalamus within the medial forebrain bundle. Cells of the zona incerta and thalamus were also sensitive to ethanol. Cells of the cerebral cortex appear to be relatively less sensitive. Many of the ethanol sensitive cells also responded to angiotensin II and when tested the effects were potentiated by Na.

Angiotensin II↗

Effects of norepinephrine applied to the lateral hypothalamus on schedule induced polydipsia.

Intrahypothalamic injections of 3 doses of norepinephrine were administered to rats under conditions of 80 percent body weight reduction (prepolydipsia), 80 percent body weight reduction (schedule induced polydipsia), and normal body weight (postpolydipsia). The only significant reduction in water intake occurred with the highest dose of norepinephrine, under the prepolydipsic condition. The fact that norepinephrine failed to block schedule induced polydipsia indicates that this behavior is regulated by a different biochemical system than that of deprivation induced drinking.

Animals↗

Ethanol and diazepam inhibition of hippocampal LTP is mediated by angiotensin II and AT1 receptors.

Angiotensin II (AII) inhibits the induction of hippocampal long-term potentiation (LTP), a frequency-dependent model of learning and memory. These results demonstrate that the dose-dependent inhibition of LTP due to ethanol (EtOH) and diazepam (DZ) involves AII. Inhibition of LTP induction by AII, EtOH, and DZ can be blocked by AII receptor antagonists saralasin and lorsartan (DuP 753). Lorsartan is a competitive antagonist of the AT1 subtype AII receptor. Therefore, the EtOH and DZ inhibition of LTP induction is mediated by AT1 receptors. These results indicate a new role for AII in the brain in the possible mediation of memory deficits associated with alcohol and the benzodiazepines.

Animals↗

Effects of free Ca2+ on the [Ca2+ + Mg2+]-dependent adenosinetriphosphatase (ATPase) of Alzheimer and normal fibroblasts.

Differences between Alzheimer and control fibroblast [Ca2+ + Mg2+]-dependent ATPase activity at free Ca2+ concentration considerably higher than physiologic concentrations were observed. At 50 microM free Ca2+, Alzheimer and control fibroblast homogenates exhibited maximum velocity values ranging from 8 to 25 nmoles phosphate released/min/mg protein. Higher free Ca2+ (350 microM) inhibited control fibroblast ATPase activity approximately 77%; whereas, Alzheimer fibroblasts retained greater than 75% starting activity. Although the pathophysiological significance of these findings is at present unclear, these data suggest the Ca2+ pump of Alzheimer fibroblasts behaves differently in the presence of high free Ca2+. Such behavior may be of potential diagnostic value.

Alzheimer Disease↗

Effect of visceral afferent activation on leg extension induced by sciatic afferent stimulation.

In cats under light chloralose and sodium pentobarbital anesthesia the effects of electrical stimulation of various visceral afferent nerves on leg extension induced by sciatic afferent stimulation were studied. Stimulation of the central end of the cervical vagus and stellate ganglion produced inhibition of induced leg extension while stimulation of the distal end of the thoracic vagus, coeliac ganglion, and splanchnic nerves produced facilitation. Decortication slightly reduced the inhibitory effect and greatly reduced the facilitatory effect. Additional decerebration greatly reduced the inhibitory effect and almost abolished the facilitatory effect. Spinal transection at C1 completely abolished the inhibitory and facilitatory effects on induced leg extension. These results suggest that visceral afferents facilitate sciatic induced leg extension principally through the cortex while they inhibit extension through the midbrain and hypothalamus.

Afferent Pathways↗

Effects of intragastric water infusion and gastric distension on hypothalamic neuronal activity.

The effects of gastric water infusion and distension were examined in neurons from various parts of the rat brain. Neurons in the lateral preoptic-lateral hypothalamic-medial forebrain bundle (LPA-LH-MFB) neuropil were sensitive to gastric water infusion and distension. Cells randomly selected and examined in other brain areas were less sensitive to the same stimulation which indicated that the effects were relatively specific. The results, in terms of changes in neuronal discharge frequency from an established baseline, indicate that many cells in the lateral preoptic-lateral hypothalamic-medical forebrain bundle area are affected by intragastric water infusion and gastric distension within a time period during which changes in drinking would normally occur. These neurons were also affected differentially by acute water deprivation. LPA-LH-MFB neurons in 24 hr water deprived animals were significantly more sensitive to water infusions and less sensitive to stomach distension when compared to cells recorded in animals maintained on ad lib eating and drinking. Some of these same neurons were also sensitive to changes in the extracellular concentrations of sodium and glucose. The results are discussed in terms of the involvement of the lateral preoptic-lateral hypothalamic-medial forebrain bundle neuropil in ingestive behavior.

Animals↗

Effects of microiontophoretically applied chemicals on hypothalamic neural activity.

Seven barrel electrodes were utilized to record simultaneously from and apply chemicals to single neurons in the hypothalamus of anesthesized male hooded rats. When a stable baseline discharge frequency was established for lateral preoptic area (LPA) or lateral hypothalamic (LH) neurons, glutamate, norepinephrine, acetylcholine, glucose and sodium were administered microiontophoretically. In addition, the effects of microiontophoretically administered chemicals and LPA or LH electrical stimulation on hypothalamic neural activity were in some cases determined for the same neuron. Recordings from 53 hypothalamic neurons indicate that the direct application of these chemicals affect LPA and LH neural activity at relatively low ejection currents in a dose related manner. In the LPA, glutamate which has a nonspecific effect and increased the discharge frequency in 96% of the cells tested, was used to establish the reliability of the techniques and baseline. Norepinephrine decreased (73%), acetylcholine increased (28%) and decreased (12%), glucose increased (12%), and sodium increased (4%) discharge frequency. In the LH, glutamate increased (91%), norepinephrine decreased (33%), acetylcholine increased (50%) and decreased (14%), glucose increased (12%) and decreased (6%), and sodium increased (20%) discharge frequency. Also, significant relations between chemical and electrical stimulation suggest that norepinephrine and possibly acetylcholine might be involved in the interactions between the LPA and LH neurons. Results are discussed in terms of the neurochemical modulation of ingestive behavior.

Acetylcholine↗

Ethanol-diazepam interactions on delayed match-to-sample performance in baboons.

Four juvenile male baboons were trained on a delayed match-to-sample (MTS) discrimination task. Single administration of 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 mg/kg diazepam (DZ) resulted in a dose-related increase in mean response time (MRT), with a maximum effect at 2.0 mg/kg. Administration of 0.25 mg/kg of DZ had no effect. Response time was increased significantly by 1.0 g/kg of ethanol (EtOH) but was not affected by 0.5 g/kg EtOH. There were no significant effects on the number of correct responses. Combined treatment of 0.5 g/kg of EtOH with 1.0 mg/kg DZ produced the same increase in MRT as the DZ alone. When 1.0 g/kg EtOH was administered with 0.25 mg/kg DZ. MRT decreased which was a significant improvement in performance as compared to the increase in MRT observed with either the EtOH or the DZ alone. Combined doses of 1.0 g/kg EtOH and 0.5 mg/kg DZ produced essentially the same increases in MRT as either dose alone. Similar results were obtained when 1.0 g/kg EtOH and 1.0 mg/kg DZ were combined and the increase in MRT was about the same for DZ alone and more than twice as great for the EtOH alone. Combined administration of the drugs had no significant effects on the number of correct choices. Since the administration of a combination of a low dose of DZ with EtOH appeared to prevent the increases in MRT observed with either drug alone and there were no observable effects on the number of correct response, these effects do not appear to involve cognitive processes but might be related to excitability changes in motor systems.

Animals↗

Role of the paraventricular nucleus in the projection from the nucleus of the solitary tract to the olfactory bulb.

Electrophysiological experiments were performed on anesthetized rats to determine the effects of lesions of the paraventricular nucleus on the amplitude of evoked potentials recorded in the periglomerular layer of the olfactory bulb after nucleus of the solitary tract electrical stimulation. Lesions of the paraventricular nucleus enhance the amplitude of both the positive and negative components of the evoked potential in the olfactory bulb. The pathway from the paraventricular nucleus to the olfactory bulb seems to exert a suppressive influence over the projection from the nucleus of the solitary tract to the olfactory bulb under these conditions.

Animals↗

Determination of free calcium.

A computer program designed to be user friendly is described in this report. Two types of calculations are provided: a) determination of free calcium concentration based on known total salt concentration and b) those which calculate total salt concentration required to insure a desired free calcium concentration in the buffered system. The user can choose up to 10 different ligands, nine different cations (known total concentration) and 10 concentrations (either free or total) of the variable cation (e.g. calcium) per calculation. Thus, this program does not restrict its user to one or two parameters (e.g., buffer and/or ions). Data generated using this method are in excellent agreement with those derived using programs in current use.

Algorithms↗

Responses of lateral hypothalamic neurons recorded in vitro to moderate changes in glucose concentration.

Single unit neuronal activity of lateral hypothalamic neurons was recorded extracellularly in hypothalamic slices. Glucose concentration in the perfusate was modified in small amounts to simulate normal physiological glycemic fluctuations associated with feeding. Several neurons responded reliably under these conditions. These data on simulated small glycemic changes, based on observations in the whole animal, suggest that the modulation of neuronal activity reported in this study is a result of a direct action of glucose on cells in this region of the hypothalamus.

Animals↗

Ethanol and diazepam interactions on conflict behavior in rats.

Twenty-four adult male rats trained on the Geller-Seifter conflict procedure received: 1.0, 2.0, or 4.0 mg/kg diazepam at 15 min, 0.25, 0.5, 1.0, 2.0, or 4.0 g/kg of ethanol (EtOH) at 30 min prior to the test session, or combinations of the same diazepam doses and 0.5 g/kg of EtOH. Ethanol administration produced a significant (p less than 0.05) dose-related decrease in lever pressing during the periods prior to the introduction of the tone stimulus, compared to lever pressing during the corresponding control periods on the day prior to drug treatment. During the posttone periods 0.25 g/kg increased lever pressing (p less than 0.05), while doses of EtOH from 0.5 to 4.0 g/kg resulted in significantly lower levels of lever pressing in periods following the discontinuation of the tone. In the presence of the conflict evoking tone stimulus, rats treated with 2.0 g/kg of EtOH increased their rate of lever pressing, while animals receiving the other EtOH doses exhibited lever pressing comparable to that observed during the corresponding control periods. Administration of EtOH had no effect on the number of reinforcements received during the entire test session, except for a significant (p less than 0.05) reduction at the highest dose of 4.0 g/kg. Diazepam increased the number of reinforcements received during the entire test session as compared to those obtained during control sessions. Lever pressing was not affected by diazepam treatment during pretone or tone periods. During the posttone periods responses were significantly (p less than 0.05) increased in rats receiving the lowest dose of 1.0 mg/kg of diazepam but the other doses were without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Interactive effects of diazepam and ethanol on baboon match-to-sample performance.

Four juvenile male baboons were trained to perform a match-to-sample (MTS) discrimination task. Diazepam (DZ) at doses of 0.5, 1.0, 2.0, 4.0, or 6.0 mg/kg resulted in a significant (p less than 0.05) increase in the mean response times (MRT) during the 2 hr test session in terms of percent change from baseline performance under nondrug conditions measured the day prior to drug treatment. Effects were maximal at 2.0 mg/kg diazepam and no further effects were observed at 4.0 or 6.0 mg/kg. Administration of 0.25 mg/kg of diazepam had no effect on MTS performance. Exposure to 0.5 g/kg of ethanol (EtOH) had no effect on response time, while 1.0 g/kg EtOH significantly (p less than 0.05) increased response time. Baboons receiving combined treatment with 0.5 or 1.0 g/kg EtOH plus 1.0 mg/kg diazepam displayed a significant (p less than 0.05) percent increase in mean response time compared to that observed under baseline conditions on the day prior to drug treatment. The 0.5 g/kg EtOH and 1.0 mg/kg diazepam combination increased MRT to an extent comparable to the effect observed at the same dose of diazepam alone. Effects observed with 1.0 mg/kg diazepam and 1.0 g/kg EtOH were similar to those produced by the DZ alone. Combinations of 0.5 g/kg EtOH and 0.5 mg/kg diazepam, 1.0 g/kg EtOH and 0.25 mg/kg diazepam, and 1.0 g/kg EtOH and 0.5 mg/kg diazepam had no significant effect on response times.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ethanol and chronic diazepam interactions on conflict behavior in rats.

Four groups of five rats each received training on the Geller-Seifter procedure and then received 0.5, 1.0 or 2.0 mg/kg diazepam (DZ) or vehicle, respectively, 15 min prior to the behavior sessions for 14 days. On Day 14 of DZ treatment rats also were administered 2.0 g/kg of ethanol (EtOH) 30 min prior to testing. Significant dose-related decreases in lever pressing occurred between groups over the 13 days of DZ treatment during the pre- and posttone periods. However, a significant effect attributable to days occurred only in the pretone period. During the tone period, the dose-related effects were greater but the variability also increased and specific contrasts between individual means were not significant. The largest increases in lever pressing associated with an anxiolytic effect occurred with 1.0 mg/kg of DZ at Day 6. On Day 14, all animals received 2.0 g/kg of EtOH and their performance was compared to performance on Day 13. During the pre- and posttone periods, the EtOH resulted in significantly less lever pressing in the control, 0.5 and 2.0 mg/kg DZ groups, indicating a sedative effect. Rats treated with 1.0 mg/kg of DZ did not exhibit this EtOH reduction in lever pressing. During the tone or conflict period, a significant dose-related increase in lever pressing due to the EtOH was observed. The increase in the control group was not significant. During repeated exposure to DZ there was a small but significant decrease in number of reinforcements which was enhanced by the EtOH at the 0.5 and 2.0 mg/kg DZ doses but not at 1.0 mg/kg DZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗