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J D Lambert

Publications and source records attributed to J D Lambert.

At least 55 records · Page 3Linked to original sources
PubMed1990

GABAB receptors play a major role in paired-pulse facilitation in area CA1 of the rat hippocampus.

Extracellular recordings of field potentials in area CA1 of the rat hippocampal slice have been used to investigate paired-pulse facilitation. Field potentials were evoked by maximal stimulation of the Schaffer collateral/commissural fibres. The height of the population spike (PS) in stratum pyramidale (str. pyr.) and the area under the field excitatory postsynaptic potential (EPSP) following the PS in the stratum radiatum (str. rad.) were quantified. These values were used to describe the time course of paired-pulse facilitation. Facilitation of the PS was maximal 50 ms after the conditioning pulse and was present over a period of about 500 ms. However, facilitation of the late area (LA) of the field EPSP was maximal afer 125 ms and had an overall duration of 1-2 s. The N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonovaleric acid (APV), had no effect on paired-pulse facilitation of either the LA or the PS. The gamma-aminobutyric acid-B (GABAB) agonist baclofen increased facilitation of the PS. This was mainly due to a reduction of the unconditioned response. Facilitation of the LA was reduced by both baclofen and the GABAB antagonist, 2-OH-saclofen. Baclofen increased the LA of the unconditioned response, while this was unaffected by 2-OH-saclofen. The LA of facilitated responses was decreased by 2-OH-saclofen while the effect of baclofen on these responses was more complex. Baclofen reduced the LA of maximally facilitated responses, while the LA of slightly facilitated responses was increased. The results show that different mechanisms are involved in the facilitation of the LA and the PS. Furthermore, activation of GABAB receptors makes a large contribution to paired-pulse facilitation of the field EPSP. It is also suggested that recording of extracellular fields in str. rad. in response to paired-pulse stimulation provides a simple electrophysiological model for testing the effect of agents which act at the GABAB receptor.

2-Amino-5-phosphonovalerate↗
PubMed1990

The slow inhibitory postsynaptic potential in rat hippocampal CA1 neurones is blocked by intracellular injection of QX-314.

Intracellular recordings were made from CA1 pyramidal neurones in the rat hippocampus slice preparation. The recording electrodes contained potassium acetate (4 M) with or without the quaternary lidocaine derivative, QX-314 (50 mM). Both fast (f) and slow (s) inhibitory postsynaptic potentials (IPSP) were evoked by low-frequency orthodromic stimulation. The s-IPSP was rapidly reduced by QX-314 injection. It decreased along a similar time course to the dV/dt of the action potential (AP). The f-IPSP and excitatory postsynaptic potential were not significantly reduced in size at a time when the s-IPSP was virtually abolished by QX-314. It is concluded that conductance through the K+ channels which are coupled to GABAB receptors is readily blocked by QX-314, while the Cl- channels which are coupled to GABAA receptors and the cation channels coupled to the glutamate receptors are relatively resistant to the local anaesthetic.

Action Potentials↗
PubMed1990

Effects of lowering [Na+]o and [K+]o and of ouabain on quisqualate-induced ionic changes in area CA1 of rat hippocampal slices.

Changes in extracellular ([Na+]o) and calcium ([Ca2+]o) concentration evoked by quisqualate (Quis), applied iontophoretically, were measured in rat hippocampal slices. Following an initial decrease in [Ca2+]o, Quis causes a post-application overshoot, which may reflect Ca2+ extrusion from cells by the Na+/Ca2+ exchanger. To test this hypothesis, the effects of directly and indirectly reduced transmembrane Na+ gradients on these Quis-induced Ca2+ overshoots were investigated. In all cases the post-application overshoots were reduced. This suggests that the Na+/Ca2+ exchanger is involved in the production of these Quis-induced Ca2+ overshoots which may have important implications for understanding how various types of glutamate receptors differ in their capability to trigger Ca2(+)-activated processes.

Animals↗
PubMed1990

The role of excitatory amino acid receptors in the propagation of epileptiform discharges from the entorhinal cortex to the dentate gyrus in vitro.

The relationship between epileptiform events in the medial entorhinal cortex (MEC) and the dentate gyrus was investigated using a slice preparation from rat brain. Simultaneous intracellular recordings were made from neurones in layer II of the MEC and neurones in the granule cell layer of the dentate gyrus (DGC). Epileptiform activity was induced by perfusion with Mg+(+)-free medium or GABAA-receptor blockers. Epileptiform discharges in MEC cells were reflected on a one-to-one basis and at a latency of 1-3 ms by depolarizing events in DGC. The latter rarely gave rise to action potentials. Bath perfusion of the N-methyl-D-aspartate (NMDA) receptor blocker, 2-aminophosphonovalerate (2-AP5) abolished the Mg+(+)-free induced events in MEC cells and the corresponding depolarizations in the DGC but local application of 2-AP5 to the dentate gyrus only reduced the depolarizations. The non-NMDA-receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whether bath applied or applied locally to the DG, had little effect on the cortical events but strongly reduced the depolarizations of the DGC. The discharges induced in MEC cells by GABA-blockers were reduced by bath applied 2-AP5 but abolished by CNQX. These effects were mirrored in the dentate gyrus by a reduction in the depolarizing events by 2-AP5 and their abolition by CNQX. Local application of either antagonist to the dentate gyrus reduced but did not abolish the depolarizations. Thus, Mg+(+)-free induced events in MEC depend mainly on enhanced NMDA-receptor activity, while events induced by bicuculline are primarily dependant on non-NMDA receptors. The depolarizing events in the DGC which reflect the activity in the EC are mediated by both types of receptor, although non-NMDA receptors play a much greater role.

2-Amino-5-phosphonovalerate↗
PubMed1990

Synchronous discharges in the rat entorhinal cortex in vitro: site of initiation and the role of excitatory amino acid receptors.

A slice preparation was used to study the spread of epileptiform activity in the rat entorhinal cortex. Interictal-like discharges were induced in the medial entorhinal cortex by blocking synaptic inhibition mediated via GABAA-receptors. Recorded intracellularly, these discharges consisted of an initial paroxysmal depolarizing shift followed by a variable number of afterdischarges. There was no apparent difference between these events whether they were recorded in isolated cortical slices or in slices where the hippocampus and subicular complex remained attached. The events were also unaffected by droplets of a xylocaine solution applied to sites in the hippocampus, subicular complex or superficial layers of the entorhinal cortex but applications to layer IV/V, lateral or medial to the recording site could reduce the number of afterdischarges without affecting the initial paroxysmal shift. Simultaneous intracellular recordings from neurons in layer IV/V and layer II of the medial entorhinal cortex showed that the paroxysmal depolarizing shift and all afterdischarges in the deeper layer always preceded those recorded in the superficial layer, and these events invariably occurred on a one-to-one basis. This was true whether the events were evoked or occurred spontaneously. The delay varied between 2 and 11 ms but was consistent for a given cell pair. A similar relationship existed between discharges recorded simultaneously in layer IV/V neurons and layer VI neurons, events in the layer IV/V cells preceding those in the deeper layer. Discharges recorded simultaneously in pairs of layer IV/V neurons showed more complex relationships. Paroxysmal depolarizing shifts were always recorded in both cells and the discharge could occur at the more medial site before the more lateral, or vice versa. For a given pair the temporal relationship was invariable. It was often the case, however, that the temporal relationship between afterdischarges was reversed with respect to the initial paroxysmal shift. This relationship was also invariable in a given pair of cells. Interictal-like discharges in layers II or IV/V neurons could be abolished by perfusion with 6-cyano-7-nitro-quinoxaline-2,3-dione which is an antagonist for the non-N-methyl-D-aspartate (i.e. quisqualate/kainate) subtype of excitatory amino acid receptor. The afterdischarges associated with the events were abolished in an all-or-none fashion whereas the blockade of the paroxysmal depolarizing shift was progressive. Antagonists of N-methyl-D-aspartate receptors also abolished afterdischarges but only reduced the initial paroxysmal shift. It is concluded that the interictal-like discharges arise intrinsically within the cortex and are not influenced by input from hippocampal or subicular structures.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

A reevaluation of excitatory amino acid-mediated synaptic transmission in rat dentate gyrus.

1. Intracellular recordings were made from granule cells in combined slices of the hippocampus and parahippocampal cortex from adult Wistar rats. The neurons had a mean resting membrane potential (EM) of -85.1 +/- 0.7 (SE) mV, input resistance (Rin) of 30.9 +/- 1.5 M omega and action potential (AP) amplitude of 79.9 +/- 1.06 mV measured from the threshold potential. The threshold for AP generation was approximately 40 mV positive to EM. 2. The passive current-voltage relationship showed anomalous rectification, with Rin increasing by 34% on average at modest depolarizations. With large excursions of the EM (by +/- 30 mV or more), there was a marked fall in Rin. 3. With extracellular recording, a monophasic, positive-going field potential of 5-15 mV was evoked by stimulation of the perforant path (PP). Intracellularly, an excitatory postsynaptic potential (EPSP) of up to 40 mV in size was recorded. It was unusual to evoke an AP on orthodromic stimulation. Perfusion with picrotoxin (PTX, up to 20 microM) had small and variable effects on the EPSP, which implies that GABAergic inhibition does not play a major role. 4. Tonic depolarization reduced the EPSP. Hyperpolarization either had no effect or again decreased the EPSP. 5. The role of excitatory amino acid (EAA) receptor subtypes in mediation of the EPSP was investigated. Perfusion with the non-N-methyl-D-aspartate (NMDA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) caused a dose-dependent reduction of the EPSP with a shift to the right of the input-output relationship. The ED50 for this effect was approximately 2 microM. 6. In the presence of 5-10 microM CNQX a small component of the EPSP usually remained, which could be blocked by the NMDA receptor antagonist +/- 2-amino-5-phosphonovaleric acid (APV, 20-50 microM). This depolarizing component was markedly enhanced during perfusion with Mg2(+)-free medium. It increased in size and duration when the membrane was depolarized and decreased with hyperpolarization. These properties are consistent with the mediation of this potential via NMDA receptors. 7. These results indicate that NMDA receptors contribute to transmission at the synapse between the PP and the granule cell. This was confirmed by demonstrating that APV caused a small reduction in the size of the untreated EPSP and a shortening of the recovery phase.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1989

Activation of N-methyl-D-aspartate receptors contributes to the EPSP at perforant path synapses in the rat dentate gyrus in vitro.

The excitatory postsynaptic potential (EPSP) evoked in the granule cells of the rat dentate gyrus following low frequency stimulation of the perforant path has been investigated using intracellular recording. The EPSP was reduced by low microM concentrations of the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). A small CNQX-resistant component of the EPSP remained. This could be blocked by the NMDA receptor antagonist (+/-)-2-amino-5-phosphonovalerate, was enhanced in Mg2+-free medium and showed a potential-dependency characteristic of the activation of NMDA ionophores. These results demonstrate that NMDA receptors contribute to the EPSP in the granule cell.

2-Amino-5-phosphonovalerate↗
PubMed1989

The molluscicidal activity of Phytolacca dodecandra. I. Location of the activating esterase.

A number of methods have been used to extract molluscicidal saponins from the dried berries of Phytolacca dodecandra. The potency of the extract has been determined to depend on the release of an enzyme found only in the seed and breaking the seed is critical to the extraction process. The enzyme is inactivated by heat of alcohol. The highest potency extract is made from a cold water extraction of finely ground dried berries.

Animals↗
PubMed1989

Corticosteroid biosynthesis in the interrenal cells of the teleost fish, Oreochromis mossambicus.

Applying high-performance liquid chromatography and thin-layer chromatography to separate corticosteroids, we studied the biosynthesis of steroids by the interrenal cells of the head kidneys (the adrenocortical homolog) of Oreochromis mossambicus. Intact head kidneys converted exogenous 17 alpha-hydroxyprogesterone into mainly cortisol, but 11-deoxycortisol, cortisone, and androstenedione were also recovered from the medium. Incubation of intact tissue with pregnenolone in addition resulted in the formation of large amounts of an unidentified product, which was absent in incubations of tissue homogenates with pregnenolone.

17-alpha-Hydroxyprogesterone↗
PubMed1989

The role of excitatory amino acids in synaptic transmission in the hippocampus.

We have highlighted some aspects of the action of excitatory amino acid transmission in the hippocampus. Fast epsps can be blocked by CNQX to reveal a component of synaptic transmission which is mediated by NMDA receptors. Extracellular recordings of ionic activities show that NMDA and non-NMDA ionophores are permeable to the major monovalent cations, while NMDA ionophores also appear to be permeable to Ca2+. Interactions of agonists applied by iontophoresis may be correlates of phenomena such as LTP, which can be evoked by appropriate synaptic stimulation.

Amino Acids↗
PubMed1989

Effects of new non-N-methyl-D-aspartate antagonists on synaptic transmission in the in vitro rat hippocampus.

1. The effects of new, potent non-N-methyl-D-aspartate (NMDA) receptor antagonists, 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), have been examined using intra- and extracellular recordings in the hippocampal slice preparation. In terms of potency and selectivity, the action of the two blockers was similar and CNQX was used in most experiments. 2. CNQX reduced the responses to ionophoretic applications of the non-NMDA agonists kainate (KAI) and quisqualate (QUIS) with IC50 values of 1.2 and 4.8 microM, respectively. In Mg2+-free solutions responses to NMDA were generally not affected by concentrations of CNQX up to 25 microM. 3. The action of CNQX was only slowly and poorly reversible on washing. Responses to QUIS and KAI were also reversibly reduced by ionophoretic application of CNQX. 4. CNQX blocked the evoked EPSP in CA1 and CA3 neurones with an IC50 of around 2 microM, which is similar to the IC50 for responses to KAI. CNQX was without effect on the passive membrane properties, the afferent volley and paired pulse potentiation. 5. In the presence of CNQX (greater than 5 microM) a small EPSP remained which was largest in CA1 neurones. It was blocked by low concentrations of the NMDA receptor antagonist (+/-)-2-amino-5-phosphonovaleric acid (APV), was markedly enhanced on removing Mg2+ ions from the bathing medium and, in voltage-clamp experiments, showed a potential dependence which is characteristic of the NMDA ionophore. 6. The latency of the APV-sensitive EPSP in CA1 was the same as the CNQX-sensitive EPSP, indicating that NMDA receptors participate in monosynaptic excitation. 7. Feedback and feed-forward inhibition in both area CA1 and CA3 were sensitive to CNQX. There seemed to be two components of the inhibition, both of which appear to be GABAergic since they could be blocked by picrotoxin (PTX), but only one of which was blocked by CNQX. The CNQX-resistant IPSP was not affected by APV. 8. In conclusion, quinoxalinediones have been used to demonstrate that non-NMDA receptors mediate the majority of the EPSP. Additionally, a component of the EPSP in CA1 is mediated by NMDA receptors and is manifested at resting membrane potentials and in the presence of Mg2+.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1988

Direct demonstration of an N-methyl-D-aspartate receptor mediated component of excitatory synaptic transmission in area CA1 of the rat hippocampus.

The action of a new non-N-methyl-D-aspartate (NMDA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), on synaptic transmission in area CA1 of the rat hippocampus has been examined. Intracellular and extracellular recordings showed CNQX to be a potent antagonist of synaptic potentials evoked by stimulation of the Schaffer collateral-commissural fibre system. One to 2 microM CNQX was sufficient to reduce the excitatory postsynaptic potential (EPSP) by 50%. CNQX is therefore about 100 times more potent than previously available non-NMDA receptor antagonists. In the presence of CNQX, a small depolarizing potential could still be evoked. This potential was sensitive to the NMDA-receptor blocker, 2-amino-5-phosphonovaleric acid (APV), increased in size on depolarizing the neurone and also increased in size on removing Mg2+ from the perfusing medium. This residual EPSP therefore has characteristics which are consistent with its mediation via the NMDA receptor-coupled ionophore. These results indicate a dual composition of the monosynaptic excitatory potential in area CA1.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1987

Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices.

The effect of low extracellular Mg2+ concentration ([Mg2+]o) on neuronal activity was studied in rat hippocampal slices. After 20-40 min of perfusion with Mg2+-free medium, when [Mg2+]o declined to approximately 0.1-0.4 mM, spontaneous field potentials developed in the CA1 and CA3 regions, but not in the dentate gyrus. In the CA3 pyramidal cell layer, these potentials consisted of repetitive (0.3-0.5 Hz), 40- to 120-ms-long positive deflections (2-5 mV) with superimposed population spikes. In the stratum (str.) pyramidale of the CA1 region, positive-negative deflections (less than 3 mV) lasting for 30-80 ms were observed, which occurred with a frequency of 0.3-0.5 Hz. In some cases, longer lasting and rapidly recurring events were also observed. In CA3 pyramidal cells, the intracellular correlates of the field potential transients were 20- to 30-mV paroxysmal depolarization shifts (PDS) with superimposed bursts of action potentials, followed by large (greater than 10 mV), 500- to 1,200-ms-long afterhyperpolarizations (AHP). In contrast, pyramidal neurons of the CA1 area did not show PDSs; instead, sequences of excitatory postsynaptic potentials (EPSPs)/inhibitory postsynaptic potentials (IPSPs) accompanied the transient field potential changes. Occasionally, spontaneous EPSPs/IPSPs, occurring with high frequencies, could also be observed in CA1 without any field potential transients. In both hippocampal regions, the epileptiform activity evolved without significant alterations in the resting membrane potential (RMP) and input resistance (RN) of the neurons, although a 2- to 5-mV reduction in action potential threshold was noted. The spontaneous activity in Mg2+-free medium was readily suppressed by raising the extracellular Ca2+ concentration ([Ca2+]o) from 1.6 to 3.6 mM. The perfusion of 10-30 microns DL-2-amino-5-phosphonovaleric acid (2-APV), an antagonist for the glutamate receptors of the N-methyl-D-aspartate (NMDA) type, also attenuated or reversibly blocked the spontaneous activity. Surgical isolation of area CA1 from CA3 ceased the occurrence of the transients in CA1 but not in CA3. The synaptic input/output curves were shifted to the left in the absence of [Mg2+]o. Threshold intensity for eliciting population spikes was 50-75% of that in normal medium. Paired-pulse facilitation was still present near threshold, but was reduced at higher stimulus intensities. Decreases in [Ca2+]o, produced by repetitive stimulation (20-Hz/5-10 s) of the Schaffer collateral/commissural pathway and monitored with ion-selective microelectrodes in the CA1 region, were enhanced in Mg2+-free medium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Epileptiform activity in combined slices of the hippocampus, subiculum and entorhinal cortex during perfusion with low magnesium medium.

Reduction of [Mg2+]o induced spontaneous epileptiform activity consisting of 40-100-ms bursts of population spikes in hippocampal slices. This activity disappeared from area CA1 when the connections to area CA3 were cut, but persisted in isolated minislices of area CA3. Spontaneous activity was also observed in the dentate gyrus, provided that the connections to the subiculum and entorhinal cortex (EC) were intact. In the parasubiculum and EC longer lasting epileptiform events were observed which resembled seizure-like behaviour. The epileptiform activity was completely suppressed by 2-aminophosphonovalerate (30 microM) suggesting that N-methyl-D-aspartate receptors for excitatory amino acid transmitters participate in the generation of this activity. These findings show that the EC possesses properties which permit the generation of seizure-like activity in contrast to the hippocampus where the activity resembled recurrent interictal events.

Action Potentials↗
PubMed1986

Electrophysiological studies in cultured mouse CNS neurones of the actions of an agonist and an inverse agonist at the benzodiazepine receptor.

The action of agents which bind with the benzodiazepine (BZ) receptor has been investigated by use of intracellular recordings from dissociated mouse neurones grown in tissue culture. The agents tested were midazolam (an agonist at the BZ receptor) and methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM-an inverse agonist at the BZ receptor). These were applied to the neurone under study by one of the following methods: iontophoresis; pressure application of known concentrations from blunt pipettes; directly in the perfusing medium. On only very few occasions did midazolam or DMCM have a direct effect on the membrane potential (EM) or conductance (GM) of the impaled neurone. For the neurones where direct effects were present, there was no consistent pattern of response. Neither substance affected the threshold for action potential generation. The effect of midazolam and DMCM on responses evoked by iontophoretic application of gamma-aminobutyric acid (GABA) was also investigated. Three parameters were used to quantify GABA responses: the depolarization (VGABA); the increase in GM (gGABA) measured with constant current pulses; using voltage clamp, the GABA current (IGABA). The GABA response should be quantified by a parameter which is linearly related to the number of GABA-operated channels which are conducting at any instant. VGABA does not fulfil this criterion. gGABA is an appropriate parameter, but is difficult to determine for large responses where the membrane is nearly short circuited. IGABA measured during voltage clamp fulfils this criterion. Midazolam (greater than 10(-6) M) reliably potentiated GABA responses with a parallel shift to the left of the dose-response curve. This is in agreement with biochemical studies where BZs increase the affinity of the GABA receptor for its ligand. The effect of DMCM on GABA responses was more variable. In the majority of cases GABA responses were reduced by DMCM. The threshold dose for this depression was usually around 10(-6) M, but was sometimes as low as 10(-8) M. Dose-response curves of IGABA or gGABA showed the inhibition to be of a non-competitive nature. The maximum inhibition achieved was around 70%. For a given neurone, and at doses which did not necessarily cause a reduction of the response to GABA, DMCM could antagonize the potentiating action of midazolam on GABA responses. A possible interpretation is that more than one BZ site per receptor complex must be occupied by a BZ agonist (or inverse agonist) before the functional changes for the complex as a whole can occur. Desensitization to GABA was increased by midazolam.

Animals↗
PubMed1985

The variation in action of excitatory amino acids in relation to distance of iontophoretic application to spinal motoneurones.

Intracellular recordings were made from lumbosacral motoneurones of barbiturate-anaesthetized cats. DL-homocysteate (DLH) and L-glutamate were iontophoresed extracellularly over a range of distances from the impaled motoneurone. Movement of the iontophoretic electrode unit was controlled by a micromanipulator which was advanced independently of that moving the intracellular electrode. Depolarizations to DLH were first detected at a greater distance from the impaled motoneurones (mean, 383 micron) than depolarizations to L-glutamate (mean, 165 micron). As the point of application approached the soma of the motoneurone, depolarizations developed more rapidly, were larger and the latent period of the L-glutamate depolarization became shorter. Dendritic 'hot-spots' of the depolarizing action of L-glutamate were not detected.

Animals↗
PubMed1984

Modulation of the responses to the GABA-mimetics, THIP and piperidine-4-sulphonic acid, by agents which interact with benzodiazepine receptors. An electrophysiological study on cultured mouse neurones.

Electrophysiological recordings from mouse neurones in tissue culture have been used to investigate how agents which interact with the benzodiazepine receptor modulate neuronal responses to gamma-aminobutyric acid (GABA) and its mimetics, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and piperidine-4-sulphonic acid (P4S). Experiments were performed in a physiological medium, pH 7.35 at 34-36 degrees C. gamma-Aminobutyric acid, THIP and P4S were applied by iontophoresis to neuronal somata. Responses were assessed by current-clamp or voltage-clamp recordings. Midazolam (an agonist at the benzodiazepine receptor) and the beta-carboline, methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM; an inverse agonist at the BZ receptor), were applied by pressure ejection from blunt pipettes. The potency order of the agonists was GABA greater than P4S greater than THIP. Midazolam (10(-7)-10(-5) M) potentiated responses to all three agonists to a similar extent with a shift to the left of the dose-response curve. The drug DMCM (10(-6)-10(-5) M) decreased the responses to all three agonists to a similar extent. The DMCM-induced depression was of a non-competitive nature. It has previously been proposed that THIP is a partial agonist and P4S an antagonist at the GABA receptor coupled to the benzodiazepine receptor, or that the benzodiazepine-receptor-coupled and electrophysiological GABA receptors are distinct. In the present study, responses to the three agonists were modulated to a comparable extent following manipulation of the benzodiazepine receptor. It is therefore unnecessary to invoke the above explanations to account for these results.

Animals↗