Biomedical subjects

M J Wayner

Publications and source records attributed to M J Wayner.

157 records · Page 9Linked to original sources

PubMedDate not supplied

Losartan reduces ethanol intoxication in the rat.

Results of a previous study showed that ethanol inhibition of hippocampal long-term potentiation (LTP) induction was mediated by angiotensin II (AII) and the AT1 subtype receptor because it was blocked by losartan, a specific AT1 antagonist. Because LTP is an important hippocampal function involved in the memory process and other behaviors, it is possible that losartan might block some of the directly observable ethanol-induced changes in rat behavior. Results demonstrate that losartan can effectively block some of the intoxicating effects of low doses of ethanol, 2 g/kg PO or IP. However, even a high dose of losartan 20 mg/kg IP, did not reduce significantly any of the intoxicating effects of the higher dose of 4 g/kg administered by gavage. Higher doses of ethanol might be more difficult to block because of a direct effect on the post synaptic membrane.

Alcoholic Intoxication↗

PubMedDate not supplied

Angiotensin II antagonists block ethanol effects on the aerial righting reflex.

The purpose of the present study was to determine the effects of an angiotensin II (AII) AT1 antagonist, losartan 10, 15, and 20 mg/kg IP, and the AII AT2 antagonist, PD 123319, 20 mg/kg IP on ethanol (EtOH) intoxication as measured by the aerial righting reflex in male rats. EtOH (25%), 2.0 g/kg, was administered by stomach tube under mild metaphane anesthesia and the aerial righting reflex was determined at 30-min intervals for 3.5 h. The AII antagonists were administered IP 2 h before the EtOH. There were six groups of 10 rats each: EtOH alone, 10, 15, or 20 mg/kg losartan plus ethanol, 20 mg/kg losartan plus 20 mg/kg PD 123319 plus EtOH, and 20 mg/kg losartan alone. Data were analyzed by a two-way ANOVA with repeated measures on one factor, time. Results show a clear intoxicating effect of ethanol on the aerial righting reflex that was blocked significantly by losartan in a dose-dependent way. Losartan alone had no observable effect. The administration of both antagonists, losartan and PD 123319 injected IP in two different sites, completely blocked the EtOH effect on the aerial righting reflex. The involvement of AII in the mediation of EtOH intoxication effects on the aerial righting reflex supports results of our previous studies on the effects of EtOH on open field behavior, AII impairment of the retention of an inhibitory shock avoidance response, and AII inhibition of hippocampal granule cell long-term potentiation, all of which can be blocked by losartan.

Angiotensin II↗

PubMedDate not supplied

Effects of trimethyltin on evoked potentials in mouse hippocampal slices.

The effects of trimethyltin (TMT) on responses to orthodromic stimulation in the CA1 pyramidal cell layer and dentate gyrus were investigated in mouse hippocampal slices. In both regions exposure to 10.0 microM TMT produced an 80 to 90% reduction in population spike amplitude. Smaller decreases in spike amplitude occurred after 5 microM TMT and these effects were reversible in the pyramidial cell layer. The latency of 5.0 microM effects was longer in the dentate gyrus and were preceded by a slight (20%) increase in spike amplitude. The smallest dose of TMT tested (1.0 microM) did not change response amplitude, but did increase the occurrence of multiple population spike potentials. When TMT was applied during paired-pulse stimulation of the perforant path the potentiation of the second response was not selectively reduced. The results indicate that orthodromic excitability of both pyramidal and granule cells in the mouse hippocampus is decreased by TMT with small differences occurring in latency and reversibility at certain doses.

Animals↗

PubMedDate not supplied

Air righting: role of the NMDA receptor channel and hippocampal LTP.

Air righting results in an animal turning over when it is dropped from a height in an inverted position. In the rat, air righting is a complex set of movements that depends only on an intact labyrinth and the normal vestibular input. Visual modulation of air righting does not develop until adulthood; and the ability to estimate the time to impact requires bilateral visual cues and indicates that air righting is a complex set of perceptually controlled movements and learning. The general purpose of this study was to determine the role of the NMDA receptor-ion channel on air righting and hippocampal LTP. Specifically: to measure the effects of various doses of CPP, an NMDA receptor antagonist, and MK-801, an ion channel blocker, on (a) air righting and (b) hippocampal LTP induction in medial perforant path-granule cell synapses. The following doses were used: CPP-0, 1, 5, and 10 mg/kg i.p.; MK-801-0. 0, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg i.p. Data were analyzed by appropriate ANOVAs and post hoc tests. Results were significant and demonstrate dose-dependent impairment of air righting and inhibition of LTP for both CPP and MK-801, implicating the role of the NMDA receptor and Na(+)/K(+)/Ca(2)+ channel in these effects. Air righting is a complex behavior and appears to be dependent upon NMDA mediated hippocampal LTP.

Analysis of Variance↗

PubMedDate not supplied

Effects of leptin and orexin-A on food intake and feeding related hypothalamic neurons.

The lateral hypothalamic area (LHA) and the ventromedial hypothalamic nucleus (VMH) have historically been implicated in ingestive behavior, energy balance and body mass regulation. The LHA is more closely associated with the initiation of eating; whereas the VMH mediates the cessation of eating. The parvocellular part of the paraventricular nucleus (pPVN) is also included in the suppressing mechanism. Recently, two hypothalamic peptides, orexin-A and orexin-B, localized in the posterior and lateral hypothalamic perifornical region were discovered in the rat brain and they increase food intake. Leptin, a protein encoded by an obesity gene, expressed in adipose tissue and released into the blood also affects food intake. Orexin and leptin receptors have been localized in the LHA, pPVN, and VMH. The purpose of this study was to measure food intake in the rat in response to leptin and orexin-A; and to determine their electrophysiological effects on feeding related hypothalamic neurons. Results clearly show that leptin suppresses food intake whereas orexin-A increases food intake. These differences are associated with leptin and orexin-A modulatory effects on LHA, pPVN, and VMH glucose responding neurons. In the LHA, leptin inhibits a larger proportion of both glucose-sensitive neurons (GSNs) and non-GSNs. In the pPVN, leptin increases more GSNs in comparison to non-GSNs. Whereas in the VMH, leptin increases the activity of glucoreceptor neurons (GRNs) in comparison to non-GRNs. Orexin-A had opposite effects: increases activity of GSNs more than the non-GSNs in the LHA and significantly suppresses GRNs in the VMH. In the pPVN, orexin-A had no observable effects on neurons that have a low density of orexin 2 receptors. Results are discussed in terms of hypothalamic neural circuits that are sensitive to endogenous food intake inducing and reducing substances.

Animals↗

PubMedDate not supplied

Effects of cervical vagus nerve stimulation on hypothalamic neuronal activity.

The effects of cervical vagus nerve stimulation on the activity of 56 neurons recorded in various parts of the rat brain were determined. Recordings were made from neurons in both the ipsilateral and contralateral hemispheres during vagus nerve stimulation. Both frequency, 10 to 100 Hz, and voltage, 1 to 20 V, of 0.5 msec pulses were applied to the nerve in a random manner over a 4 sec period while monitoring ongoing single neuronal activity. Frequency response relationships were established for 64% of the lateral preoptic-lateral hypothalamic-medial forebrain bundle (LPA-LH-MFB) neurons which were tested. Four types of LPA-LH-MFB neuronal responses were observed. Twenty percent of the neurons increased in discharge frequency as stimulation frequency was increased, 9% increased in discharge frequency as stimulation frequency was decreased, 23% decreased in discharge frequency as stimulation frequency was increased, and 14% decreased in discharge frequency as stimulation frequency was decreased. Increasing the stimulation voltage always enhanced the magnitude of the effects observed due to changing the stimulation frequency. Neurons observed in some other parts of the brain were not affected by the same stimulation. In addition, cells tested in the LPA-LH-MFB area which were previously tested and affected by gastric distension were also affected similarly by vagus nerve stimulation. Results are discussed in terms of peripheral afferent control over LPA-LH-MFB neuronal activity related to ingestive behavior.

Afferent Pathways↗

PubMedDate not supplied

A bipolar electrode for peripheral nerve stimulation.

The construction of a bipolar electrode for the stimulation of peripheral nerves is described. The electrode was designed for acute stimued in which the effects of peripheral nerve stimulation on central neural activity in rats were determined. Since the electrode can be secured into a fixed position, neural recordings can be made during the stimulation of various visceral nerves and the electrode can be easily adapted for chronic behavioral studies.

Animals↗

PubMedDate not supplied

Ethanol affects hypothalamic neurons projecting to the hippocampus and inhibits dentate granule cell LTP.

In previous studies we demonstrated that ethanol inhibition of hippocampal granule cell long-term potentiation (LTP) is mediated by angiotensin II (AII), and the inhibition can be blocked by losartan, a specific AII receptor antagonist. The purpose of the present study was to demonstrate that this low-dose ethanol inhibition of dentate granule cell LTP induction is mediated by lateral hypothalamic (LH) afferents that project to the granule cells. In urethane anesthetized rats, we compared the effects of ethanol infusion, 6.0 microliter/30 min, by means of an open-ended push-pull type cannula, in both the LH and the dentate gyrus, on dentate granule cell LTP. Results demonstrate a dose-dependent inhibition of LTP induction when the LH is perfused that can be blocked by losartan, 10 mg/kg i.p.. Four doses of ethanol were used: 5, 10, 20, and 30 mM. There was no effect when the dentate gyrus was infused with 30 mM ethanol and normal granule cell LTP was observed. Also, these results demonstrate for the first time a low-dose ethanol effect on a physiological function, LTP in a specific neural pathway, directly related to the anterograde amnesia produced by ethanol on short-term memory. Therefore, these data support our hypothesis that ethanol inhibition of LTP induction at the medial perforant path-granule cell synapse can be attributed to a presynaptic release of AII and cannot be explained in terms of a direct postsynaptic effect on the granule cells.

Angiotensin II↗

PubMedDate not supplied

Losartan improves the performance of ethanol-intoxicated rats in an eight-arm radial maze.

Results of previous research demonstrate that angiotensin II (Ang II) inhibits long-term potentiation (LTP) in medial perforant path-dentate gyrus granule cells and that the inhibition is mediated by the AT1 receptor because it can be blocked by losartan, a specific AT1 receptor antagonist. Ang II impairment of retention and ethanol inhibition of LTP can both be blocked by pretreatment with losartan. Because losartan pretreatment also prevents ethanol intoxication measured in terms of the aerial righting reflex, the purpose of the present study was to assess the effects of 2.0 g/kg ethanol administered by gavage on performance in an eight-arm radial maze, and then to determine the effectiveness of losartan in reducing the impairment of the learning and memory process. Results confirmed the general hypothesis that ethanol-induced cognitive deficits are mediated by Ang II and the AT1 receptor and that the impairment can be reduced by pretreatment with losartan.

Alcoholic Intoxication↗

PubMedDate not supplied

Nicotine blocks ethanol and diazepam impairment of air righting and ethanol impairment of maze performance.

Results of our previous research in rats demonstrate the following: (a) Angiotensin II (Ang II) inhibits long term potentiation (LTP) in dentate granule cell-perforant path synapses and that this inhibition can be blocked by losartan, an Ang II AT1 receptor antagonist; (b) both ethanol and diazepam inhibit LTP induction and this inhibition can be blocked by losartan; (c) impairment of air righting by ethanol and diazepam (DZ) and eight-arm radial maze performance by ethanol can be blocked by pretreatment with losartan: (d) inhibition of dentate granule cell LTP by Ang II can also be prevented by pretreatment with nicotine. Therefore, it seemed reasonable to hypothesize that ethanol and diazepam impairment of air righting and maze performance might also be blocked by pretreatment with nicotine. The purpose of the present study was to determine the effects of nicotine 0.1, 0.2, 0.3, and 0.4 mg/kg subcutaneously (SC) on 2.0 g/kg ethanol per os (PO) and 1.0 and 2.0 mg/kg DZ intraperitoneally (i.p.) induced impairment of air righting; and to determine if the impaired maze performance due to 2.0 g/kg ethanol PO could be prevented by pretreatment with 0.4 mg/kg of nicotine, SC. Results confirm the hypothesis that moderate doses of ethanol, 2.0 g/kg PO, and DZ, 1.0 mg/kg i.p. impair air righting and that the impairment can be prevented by pretreatment with nicotine SC. Nicotine was not effective in blocking the 2.0 mg/kg DZ impairment of air righting. Nicotine, 0.4 mg/kg SC, prevented the impaired maze performance induced by 2.0 g/kg ethanol PO.

Animals↗

PubMedDate not supplied

Effects of iontophoretic application of trimethyltin on spontaneous neuronal activity in mouse hippocampal slices.

Changes in spontaneous activity in various regions of mouse hippocampal slices were observed following iontophoretic application of trimethyltin (TMT). TMT (0.5 mM) dissolved in 0.15 M NaCl and ejected in 30 sec periods from four barrel micropipettes using anodal ejection currents (3-28 nA) produced dose dependent increases in the spontaneous activity of 67.6% of the 34 dentate gyrus cells tested. Seventy percent of the 25 CA3 cells tested displayed prolonged (30-200 sec) decreases in activity. The majority of CA1 and CA2 cells examined also displayed a decrease in firing rate. Repeated applications of TMT produced increased variability in spontaneous firing rates in all regions tested. When slices were maintained in a low Ca++, high Co++ perfusion fluid to inhibit synaptic activity, the TMT induced increase of dentate gyrus cell firing rate was not observed. The results demonstrate that direct application of TMT produces immediate changes in hippocampal cell activity that is specific for certain regions. Significant increases in firing rate were only observed in the dentate gyrus and these effects were calcium dependent.

Action Potentials↗

PubMedDate not supplied

Effects of triethyltin on ingestive behavior at ad lib, reduced, and recovered body weight.

The effects of repeated injections of small amounts of the neurotoxicant triethyltin (TET) on 1 and 24 hr food and water intake were investigated in rats at ad lib feeding, reduced, and recovered body weights. Following adaptation to 15% ethanol vehicle injections, TET doses of 0.5, 1.0 and 1.5 mg/kg body weight were administered in four separate injections, each separated by 3 or 4 days. Decreases only in 24 hr food intake and body weight occurred with 1.5 mg/kg TET in ad lib feeding animals. In animals reduced to 80% body weight decreases in water intake occurred for only 1 hr after injections of 1.0 or 1.5 mg/kg TET. When TET was administered to animals previously reduced to 80% body weight and allowed to recover ad lib feeding weight, effects on daily food and water intakes were observed. The effects of TET on ingestive behavior seem to be dependent on whether or not animals are or have been chronically food deprived. Results are discussed in terms of the known effects of TET on brain physiology.

Analysis of Variance↗

PubMedDate not supplied

Effects of triethyltin on schedule dependent and schedule induced behaviors under different schedules of reinforcement.

The subacute effects of triethyltin (TET) on operant responding and adjunctive behavior were assessed using either a fixed ratio (FR-30) or fixed interval (FI-1 min) schedule of reinforcement. Response rate decreased for rats on the FR-30 schedule given 1.5 mg/kg whereas animals on the FI-1 min schedule showed decreases in presses and pellets obtained at 1.5 mg/kg and in water intake at 1.0 and 1.5 mg/kg. When the animals on the FI-1 min schedule were allowed to recover body weight, decreases in presses, pellets obtained, licking, and water intake occurred at 0.5, 1.0 and 1.5 mg/kg. Schedule induced and schedule dependent behaviors were affected by low doses of TET. Rats at recovered body weight were most sensitive and affected by the lowest TET doses.

Analysis of Variance↗