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M J Rowan

Publications and source records attributed to M J Rowan.

At least 73 records · Page 4Linked to original sources
PubMed1995

Dantrolene inhibits long-term depression and depotentiation of synaptic transmission in the rat dentate gyrus.

The involvement of Ca release from intracellular stores in the induction of long-term depression and depotentiation of excitatory synaptic transmission was investigated in the rat dentate gyrus using dantrolene, an agent known to block Ca release via the ryanodine receptor. In control slices, low-frequency stimulation (1 Hz for 15 min) induced robust long-term depression of baseline field excitatory postsynaptic potentials and depotentiation of previously established long-term potentiation. Dantrolene (50 microM) was found to block completely both long-term depression of baseline responses and depotentiation. Moreover, long-term potentiation induced by high-frequency stimulation was enhanced in the presence of dantrolene.

Animals↗
PubMed1995

Potentiation of N-methyl-D-aspartate-receptor-mediated currents detected using the excised patch technique in the hippocampal dentate gyrus.

The excised patch mode of the patch-clamp technique has been used to record isolated patch N-methyl-D-aspartate-receptor-mediated currents (patch NMDA-receptor-currents) evoked by electrical stimulation in the dentate gyrus of the hippocampal slice. The patch NMDA-receptor-currents were recorded by placing a patch of membrane isolated from the cell body in the inner molecular layer of the dentate gyrus and applying stimulation to the proximal commissural/associational pathway. The patch NMDA-receptor-currents, recorded at +40 mV in the presence of AMPA-receptor and GABAA-receptor antagonists, consisted of two to six summated unitary openings of NMDA-receptor channels, lasting several hundred milliseconds. Tetanic pathway stimulation evoked a rapid increase in the amplitude of the patch NMDA-receptor-currents which lasted for a period of at least 20 min following the tetanus. The study suggests that the potentiation of the patch NMDA-receptor-currents is due to either an increase in transmitter release, or alternatively, to the release of an extracellular messenger which directly enhances NMDA-receptor responsiveness.

Animals↗
PubMed1995

Tetanically induced LTP involves a similar increase in the AMPA and NMDA receptor components of the excitatory postsynaptic current: investigations of the involvement of mGlu receptors.

Whole-cell patch-clamp recordings of evoked excitatory postsynaptic currents (EPSCs) were made from granule cells of the rat dentate gyrus in vitro. Tetanic stimulation in control media evoked a statistically identical long-term potentiation (LTP) of both the AMPA and NMDA receptor-mediated components of the dual component EPSC (AM-PAR and NMDAR EPSCs), as shown by a similar percentage increase in both components when measured at a holding potential of -30 mV, and also by an identical time course of the pre- and post-LTP induced EPSC at -30 mV and -70 mV. Application of the selective metabotropic glutamate receptor (mGluR) agonist 1S,3R-ACPD induced a transient depression followed by a rapid onset LTP of both the AMPAR and the NMDAR components of the dual component EPSC. The ACPD- and tetanically induced LTP of the AMPAR EPSC was NMDAR dependent, being abolished by the NMDAR antagonist AP5. Tetanic stimulation, and application of ACPD, also induced a relatively rapid onset LTP of the pharmacologically isolated NMDAR EPSC. Such tetanically and ACPD-induced LTP of the isolated NMDAR EPSC was also dependent on NMDAR activation, being strongly inhibited by AP5. The tetanically and the ACPD-induced LTP of the NMDAR EPSC were dependent on protein kinase C (PKC) stimulation, being strongly inhibited by the PKC inhibitor PKCI (19-31). The studies suggest that coactivation of the mGluR and NMDAR are required for induction of LTP of both the AMPAR- and NMDAR-mediated synaptic transmission. Moreover, LTP of the NMDAR-mediated synaptic transmission appears to be dependent on coincident activation of the NMDAR and mGluR.

Animals↗
PubMed1994

5-HT1A receptor-mediated inhibition in the hippocampus of the alert rat--effects of repeated gepirone treatment.

The effects of acute and repeated treatment with the 5-HT1A receptor ligand gepirone on hippocampal excitatory synaptic transmission were investigated. Recordings of the electrically evoked field population excitatory postsynaptic potentials (e.p.s.p.s) were made in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert male Wistar rats. Acute injection of gepirone reduced the e.p.s.p. amplitude in a transient dose-dependent (0.5-10 mg/kg, i.p.) manner. This effect was blocked by the 5-HT1A receptor antagonist MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl methylaminoethys]-8- azaspiro[4,5]decane-7,9-dione methyl sulphonate, 2 mg/kg, i.p.). Gepirone (1 mg/kg per day, i.p.) administered for 7 days produced a gradual reduction in the daily pre-injection baseline e.p.s.p. amplitude coupled with a concomitant reduction of the acute response to the drug. The chronic baseline reduction was transiently reversed by the 5-HT1A receptor antagonist spiroxatrine and complete recovery to pretreatment levels was observed 48 h after the last gepirone dose. The data indicate that with repeated administration, a prolongation and enhancement of the 5-HT1A receptor-mediated reduction in the e.p.s.p. by gepirone occurs. This delayed effect may contribute to the slow onset of therapeutic action of gepirone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Long-lasting enhancement of NMDA receptor-mediated synaptic transmission by metabotropic glutamate receptor activation.

Synaptic transmission mediated by the N-methyl-D-aspartate (NMDA) glutamate receptor plays a key role in a range of plastic processes in the nervous system. These include long-term potentiation of synaptic transmission mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor, neuronal development, excitotoxicity and certain learning tasks. Recently, long-term potentiation of NMDA receptor-mediated synaptic transmission was found to occur following high-frequency (tetanic) stimulation via an unknown mechanism. We show here that activation of metabotropic glutamate (mGlu) receptors by neurally released transmitter underlies this type of long-term potentiation. The whole-cell patch-clamp technique in the 'thick' slice of the rat dentate gyrus was used to measure NMDA receptor-mediated excitatory postsynaptic currents. We have found that mGlu receptor activation by a selective agonist produced a long-lasting enhancement which was mutually exclusive with long-term potentiation of these NMDA currents. Moreover, both forms of potentiation were greatly reduced by the mGlu receptor antagonists L-2-amino-3-phosphonopropionate and (R,S)-alpha-methyl-4-carboxyphenylglycine.

Animals↗
PubMed1994

Gepirone and 1-(2-pyrimidinyl)-piperazine-induced reduction of aversively evoked ultrasonic vocalisation in the rat.

Ultrasonic (22 kHz) vocalisation in response to a mildly aversive foot shock was measured in the dark compartment of a light-dark box both immediately and 24 h after the shock. Gepirone (1 and 5 mg/kg, IP) produced a reduction in the duration of vocalisation at both times. Although a metabolic inhibitor, proadifen (40 mg/kg) did not reduce this effect of gepirone, the gepirone hepatic metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP, 1 mg/kg), was also active in the test. Performance of a 24 h step-through passive avoidance task was impaired by gepirone only at a dose, 5 mg/kg, which also reduced spontaneous locomotor and rearing activity in the apparatus. It would appear that mild foot shock-evoked ultrasonic vocalisation may provide a more sensitive indicator of the effect of gepirone and related drugs on the affective response of rats to aversive stimulation.

Animals↗
PubMed1994

Adaptive changes in 5-HT1A receptor-mediated hippocampal inhibition in the alert rat produced by repeated 8-OH-DPAT treatment.

1. The effect of acute and repeated treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor ligand, on excitatory amino acid-mediated synaptic transmission was examined in the stratum radiatum CA1 region of the dorsal hippocampus of alert, gently restrained, rats. 2. Acute administration of 8-OH-DPAT transiently reduced the amplitude of the field excitatory postsynaptic potential (e.p.s.p.) in a dose-dependent (25-75 micrograms kg-1, i.p.) manner. This effect was blocked by the postsynaptic 5-HT1A receptor antagonist, MDL 73005EF (2 and 4 mg kg-1, i.p.). 3. 8-OH-DPAT (25 micrograms kg-1, i.p.) administered daily for 7 days produced a gradual reduction in the 24 h pre-injection baseline field e.p.s.p. amplitude. The reduction reached its lowest level after 7-8 days and was transiently reversed by acute injection of MDL 73005EF (2 mg kg-1, i.p.) on day 8. The field e.p.s.p. baseline amplitude recovered fully 5-8 days after cessation of drug treatment. 4. 8-OH-DPAT (25 micrograms kg-1, i.p.) administered daily for 7 days produced a marked reduction in acute response to 8-OH-DPAT (25 and 50 micrograms kg-1, i.p.) which did not recover until between day 36 and day 80 of the study. 5. It was concluded that repeated treatment with 8-OH-DPAT produced adaptive changes which resulted in a reduction in the dynamic range of 5-HT1A receptor-mediated transmission in the hippocampus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Use-dependent effects of acute and chronic treatment with imipramine and buspirone on excitatory synaptic transmission in the rat hippocampus in vivo.

The effects of acute and long-term treatment with imipramine and buspirone on the responses of rat hippocampal neurones to low and high frequency electrical stimulation were compared. Whereas acute treatment with imipramine (10 mg/kg, i.p.) had no effect on synaptic responses to low frequency stimulation, chronic treatment for 14 days significantly reduced the amplitude of the field excitatory postsynaptic potential. Both acute and chronic imipramine treatment markedly reduced the amplitude of the nerve volley and excitatory postsynaptic potential evoked at high frequency stimulation rates in a use-dependent manner. Buspirone (0.5-3 mg/kg, i.p.) produced a significant reduction of the excitatory postsynaptic potential at high frequencies. This was enhanced after repeated administration of a dose of 0.5 mg/kg for 14 days. We previously reported a similar effect of buspirone at low frequency stimulation. Both compounds therefore share the ability to exert strong depressant effects on transmission in the hippocampus especially after chronic treatment.

Animals↗
PubMed1992

Serotoninergic depression of auditory evoked responses recorded in the rat hippocampus: effect of repeated buspirone treatment.

Auditory evoked middle latency responses recorded in the hippocampus (HAER), were monitored in alert, gently restrained rats with chronic indwelling electrodes and cannulae. Intrahippocampal (i.h.) injection of 5-hydroxytryptamine (5-HT, 10 micrograms) reduced the amplitude and increased the latency of the N28 and P55 peaks of the HAER. An early (P18) negative peak was unaffected. Buspirone (1 microgram, i.h. and 3 mg/kg, i.p.) had similar effects to those produced by i.h. 5-HT. RU 24969 (1 mg/kg, s.c.) also reduced the amplitude of the N28 peak of the HAER. Long-term treatment with buspirone for 14 days at a dose (0.5 mg/kg, i.p.) which when applied acutely did not produce any observable effect, caused an increase in the latency of both the N28 and P55 peaks. Direct i.h. injection of 5-HT into these chronically treated animals did not have any additional depressant effect on the HAER peaks. It is concluded that these serotoninergic agonists can modulate the later peaks of the HAER possibly via 5-HT1A receptors. In the case of buspirone there was evidence of an enhanced depressant effect following chronic treatment [corrected].

Animals↗
PubMed1991

EEG and event related potentials in hepatic encephalopathy.

In recent years, there have been considerable developments in the application of EEG and event related potential technology to the diagnosis and assessment of hepatic encephalopathy in cirrhotic patients. A review of the literature on this subject is reported. The visually interpreted EEG is only of benefit in the late stages of hepatic encephalopathy. EEG spectral analysis allows identification of all stages of the condition. Brainstem auditory evoked responses are normal in encephalopathy. Visual evoked responses show an increase in the latency and eventual loss of individual component waves as encephalopathy progresses. Somatosensory evoked responses show a progressive prolongation of peak and inter-peak latency which correlates with the severity of encephalopathy. The auditory P300 evoked response shows an increased latency with the development of hepatic encephalopathy. Event related potentials provide objective diagnostic markers of the development of hepatic encephalopathy. The increased use of this technology in the assessment of patients with this condition should be of clinical benefit in its management.

Electroencephalography↗
PubMed1991

Change in barbiturate anaesthetic sensitivity as a prognostic indicator of electroconvulsive therapy outcome.

Barbiturate anaesthesia is modulated by brain noradrenergic (NA) function. As derangement of NA pathways is postulated to occur in depression, changes in anaesthetic sensitivity measured as producing loss of eyelash reflex were monitored in 29 depressed patients throughout a course of electroconvulsive therapy (ECT). Patients thus monitored were followed for 12 months after completing treatment. An increase in barbiturate induction dose over a course of ECT, indicating a decrease in anaesthetic sensitivity, was a powerful predictor of maintained wellbeing. All patients who increased their sensitivity to the anaesthetic either failed to respond to the course of ECT or relapsed within 12 months. The possible mechanism for this is discussed.

Anesthetics↗
PubMed1990

The auditory P300 event-related potential: an objective marker of the encephalopathy of chronic liver disease.

Recently many variants of electroencephalogram-evoked responses have been studied as potential diagnostic aids in the detection and evaluation of hepatic encephalopathy. This study assesses the value of the auditory P300 event-related potential--a slow component of the auditory evoked response--as a tool in this field. Twenty-one nonencephalopathic and 12 encephalopathic (grade 1/2) cirrhotic patients and 26 controls were assessed clinically and psychometrically. Electroencephalogram spectral analysis and visual evoked response recordings were also conducted. An auditory P300 wave was elicited using the standard two-tone discrimination paradigm. The latency and amplitude of this wave were measured. The latency of the P300 was found to be significantly increased in the encephalopathic patients compared with both nonencephalopathic cirrhotic and control groups (p less than 0.05). Amplitude of the wave was decreased in both nonencephalopathic and encephalopathic patients, but this was not statistically significant. This study suggests that the latency of the P300 is a good marker of grades 1 and 2 clinical hepatic encephalopathy. The delays in the P300 latency may indicate that encephalopathic patients have a deterioration of their stimulus evaluation abilities.

Chronic Disease↗
PubMed1990

Buspirone impairment of performance of passive avoidance and spatial learning tasks in the rat.

The effects of buspirone on the execution of step-through passive avoidance and spatial navigation learning tasks were assessed. In view of the anxiolytic properties of the drug, its effects on shock induced ultrasonic vocalizations and shock suppressed locomotor activity in a hole-board were also determined. Doses (0.5, 1 and 2 mg/kg, IP) which did not affect exploratory activity in a novel environment (light/dark box and hole-board apparatus) were used. Buspirone (1 and 2 mg/kg) impaired performance on the 24 h passive avoidance recall test when given prior to the training and the test sessions or prior to the test session only but not when given before the training trial only. The stress response to the mild footshock, as measured in terms of suppressed locomotor activity in the hole-board apparatus and post-shock ultrasonic vocalizations, was reduced by buspirone (at 1 and 2 mg/kg, respectively), indicating that its effect on behavior in the passive avoidance learning task is probably due to its anxiolytic properties. Evidence for a possible amnesic effect of buspirone (2 mg/kg) was found on the acquisition and probe test trials in the spatial navigation task. During training the latency to find a submerged escape platform in a water maze was increased. Performance on a probe test was also impaired but this effect was not apparent in animals which had received buspirone only prior to the probe test. Although these changes may be attributable to alterations in many aspects of cognitive processing, the possibility of a direct effect on memory warrants further investigation.

Animals↗
PubMed1990

Actions of 5-HT1 ligands on excitatory synaptic transmission in the hippocampus of alert rats.

1. The effects of 5-hydroxytryptamine1 (5-HT1) ligands on excitatory synaptic transmission were examined in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert, gently restrained, rats. 2. 5-HT produced a dose-dependent reduction in the amplitude of the electrically evoked population excitatory postsynaptic potential (e.p.s.p.) when injected directly into the hippocampus via a cannula (dose producing 50% maximum inhibition, ED50 = 0.46 microgram). 3. Direct intrahippocampal (i.h.) application of buspirone (ED50 = 0.29 microgram), gepirone (1 microgram), ipsapirone (1 microgram), BMY 7378 (0.1 microgram) and 5-carboxamidotryptamine (5-CT, 0.02 microgram) mimicked the inhibitory effect of 5-HT. 4. Systemic injection of buspirone (ED50 = 0.88 mg kg-1, i.p.), BMY 7378 (0.01 mg kg-1, i.p.) and RU 24969 (1 mg kg-1, s.c.) also had an inhibitory effect on the amplitude of the e.p.s.p. 5. Injection of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 2 micrograms) and spiroxatrine (1 microgram) i.h. alone had no effect on the e.p.s.p. amplitude but prevented the inhibitory effect of 5-HT. 6. Systemic injection (i.p.) of methysergide (5 mg kg-1) and spiroxatrine (1 mg kg-1) antagonized the inhibitory effect of buspirone whereas pretreatment with ketanserin (1 mg kg-1), trifluoperazine (1 mg kg-1) and idazoxan (1 mg kg-1) had no effect on the response to buspirone. 7. It is concluded that hippocampal synaptic transmission is highly sensitive to the agonist and antagonist properties of 5-HT1 ligands in the alert rat.

Adrenergic alpha-Antagonists↗
PubMed1990

Flash visual evoked responses in the early encephalopathy of chronic liver disease.

In recent years many variants of EEG sensory evoked responses have been studied as potential diagnostic aids in the detection and quantification of hepatic encephalopathy (HE). This study assesses the value of the flash visual evoked response (VER). Twenty-six controls and 21 non-encephalopathic and 12 encephalopathic (grade 1/2), biopsy-proven, cirrhotic patients were assessed clinically, psychometrically, and electrophysiologically. Flash VER from three different leads were obtained from each patient. Data from the fronto-occipital leads gave the best differentiation between the subjects. The P2 and N3 peak latencies were significantly increased in the two liver groups and correlated with the mental state and psychometric results. The N3 latency had a 92% specificity and a 50% sensitivity in the detection of grade 1/2 HE. This study suggests that the N3 latency changes may be a good marker of early clinical HE and useful in the longitudinal assessment of individual patients.

Adult↗
PubMed1989

The role of N-methyl-D-aspartate receptors in the generation of short-term potentiation in the rat hippocampus.

The effects of stimulus intensity and the N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovalerate (AP5) were studied on the induction of short-term potentiation (STP) and long-term potentiation (LTP) in CA1 of the rat hippocampal slice. A tetanus of very weak intensity stimuli produced STP, and also LTP providing the stimuli were applied in the form of a series of high frequency trains rather than one continuous train. Increasing the intensity of the stimuli to just threshold for spike initiation produced larger amplitude STP and LTP. AP5 strongly inhibited the STP as well as the LTP produced by a series of high frequency trains, indicating a large component of this STP was generated by activation of NMDA receptors. A further residual component of STP in AP5, which was associated with a decrease in paired pulse facilitation, is probably generated by a presynaptic increase in the probability of transmitter release.

2-Amino-5-phosphonovalerate↗
PubMed1989

Serotonergic involvement in the inhibitory effects of repeated buspirone treatment on synaptic transmission in the hippocampus.

The effects of acute and long-term treatment with buspirone on synaptic transmission in the hippocampus were compared in alert rats with chronic indwelling electrodes and cannula. Buspirone produced a transient dose-dependent reduction in the amplitude of the excitatory postsynaptic potential (EPSP) when acutely injected either systemically (0.3-3.0 mg/kg i.p.) or directly into the hippocampus (0.1-1.0 microgram i.h.). Whereas acute application of 0.5 mg/kg i.p. produced a 20% reduction which reversed within 2 h, during long-term treatment with this relatively low dose there was a gradual reduction of the baseline EPSP amplitude which reached a maximum (40%) between days 7-14 and which did not reverse completely until 72 h after the last injection. Intrahippocampal injection of either buspirone or 5-hydroxytryptamine did not have any additional effect during the period of baseline reduction. The 5-HT1A receptor antagonist spiroxatrine (1 mg/kg i.p.) produced a transient reversal of the effect of chronic buspirone. It is concluded that the chronic inhibitory effect of buspirone is probably an extension of its acute action on 5-HT1A receptors in the hippocampus.

Animals↗