Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GABA Modulators”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,729 records · Page 96Linked to original sources
PubMed1996

Increased food intake following injection of the benzodiazepine receptor agonist midazolam into the IVth ventricle.

Despite a prolonged period of research with benzodiazepines, the central site(s) of action for the hyperphagic effects of these compounds remains to be determined. The aim of the present studies was to examine the effect of direct administration of the benzodiazepine receptor agonist midazolam into the IVth ventricle on ingestive behavior in nondeprived rats. In Experiment 1, microinjection of midazolam (3 and 30 micrograms/microliter) into the IVth ventricle was sufficient to increase consumption of a palatable mash. In Experiment 2, the hyperphagic effect was blocked by systemic administration of the selective benzodiazepine receptor antagonist flumazenil (20 mg/kg). The results indicate that a brainstem site of action may be important for the effects of benzodiazepine receptor agonists on ingestive behavior.

Animals↗
PubMed1995

Effects of training, early handling, and perinatal flumazenil on shuttle box acquisition in Roman low-avoidance rats: toward overcoming a genetic deficit.

The present series of studies investigated the effects of intensive training, postnatal handling-stimulation and/or perinatal flumazenil (Ro 15-1788, benzodiazepine receptor antagonist) on the acquisition of two-way active avoidance by Roman low-avoidance (RLA/Verh) rats. This rat line has been selectively bred for poor avoidance in the shuttle box, while their Roman high-avoidance counterparts (RHA/Verh) have been selectively bred for their extremely good performance in that task. In the first experiment, RLA/Verh rats submitted to a long and intensive training procedure (unlike those submitted to short training) were able to achieve a performance of 56% of avoidances per session. In the second experiment both postnatal handling and perinatal flumazenil treatments increased avoidance responding in another group of RLA/Verh rats tested at the age of 18 months. Finally, in the last experiment, the performance of a third stock of RLA/Verh rats of the same age which had received perinatal flumazenil did not differ, on the later phases of training, from that shown by RHA/Verh animals. The results are discussed in terms of the "warm up" phenomena which seems to be highly involved in the selection of RLA/Verh rats, as well as on the possibility that central benzodiazepine receptors could play a role in the genetic deficit shown by RLA/Verh rats, which apparently confers a greater emotivity.

Animals↗
PubMed1995

alpha-MSH-induced behavior: changes after diazepam and baclofen administration related with cyclic AMP levels.

The present work was performed to evaluate the participation of the benzodiacepinic GABAA and GABAB components upon excessive grooming, locomotion, rearing, and stretching/yawning syndrome induced by the intracerebroventricularly alpha-MSH administration by using GABAA and GABAB agonists. It also aims at evaluating possible relation between changes in cAMP levels in caudate-putamen and accumbens nuclei and the behavioral responses. Injection of diazepam or baclofen reduced the total behavioral scores in a dose-related manner as well as the cAMP levels with respect to the control values (animals treated with artificial cerebrospinal fluid). When diazepam was tested in animals simultaneously injected with alpha-MSH, behavioral scores decreased with respect to those treated with the peptide alone. Cyclic AMP also decreased after combined treatment (MSH + diazepam).

Animals↗
PubMed1996

Effects of convulsant and anticonvulsant agents on memory in squirrel monkeys.

1. It has been reported that subconvulsive doses of convulsant agents such as strychnine and pentylenetetrazole can enhance memory in rodents studied under various behavioral procedures. The present study was designed to determine if similar results might be obtained in squirrel monkeys. 2. Responding by squirrel monkeys was maintained by food presentation under a repeated acquisition of behavioral chains procedure. Each subject acquired a different three-response chain each session. 3. Sequence completions were reinforced under a fixed-ratio 5 schedule (FR 5) and errors produced a brief timeout. After the subject reached a predetermined acquisition criterion, the session was stopped and a 24 hr delay was interposed. Following the delay, the subject was retested on the same discrimination and retention was quantified as percent savings. 4. When administered immediately after the subject reached the acquisition criterion, strychnine (0.0056 -0.18 mg/kg) and pentylenetetrazole (0.32-42 mg/kg) neither enhanced nor disrupted percent savings under the 24 hour delay. Similarly, the delta opioid agonist, BW373U86 (0.0056-3.2 mg/kg) [(+/-)-4 -((alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl -1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide dihydrochloride], had little or no effect on percent savings following a 24 hr delay. This was true even at doses of BW373U86 which produced convulsions. In contrast, triazolam (1-1.8 mg/kg) decreased percent savings following the 24 hr delay at doses which had little or no effect on response rate. 5. These results suggest that at subconvulsive doses, convulsant agents have little or no effect on memory storage, while at higher doses agents such as triazolam can disrupt memory processes in squirrel monkeys.

Animals↗
PubMed1987

Post-tetanic contractile events further support the interaction of multiple neurotransmitters in the neuroeffector junction of the rat vas deferens.

Post-tetanic events were recorded in isolated, superfused, epididymal and prostatic halves of the rat vas deferens. Increasing the frequency of nerve stimulation from 0.15 to 15 Hz (1-30 s) and then back to 0.15 Hz produced a post-tetanic potentiation (PTP) of the muscular responses in the epididymal end but a post-tetanic inhibitory response (PTI) in the prostatic half. Both effects were abolished by tetrodotoxin or animal pretreatment with 6-hydroxy dopamine (6-OHDA). PTP was markedly reduced by reserpine treatment or tissue incubation with prazosin. PTI was not altered by adrenergic drugs but partially reduced by tissue application of bicuculline or strychnine, revealing that gamma-aminobutyric acid (GABA) may modulate the motor transmission towards the prostatic half of the rat ductus.

Animals↗
PubMed1989

Adrenergic neurons in the nucleus tractus solitarius receive GABAergic synapses. Demonstration by dual immunocytochemistry in the rat.

By means of a dual immunocytochemical labeling for phenylethanolamine-N-methyltransferase and glutamate decarboxylase, synaptic associations between adrenaline-synthesizing neurons and GABAergic terminals are demonstrated in the medial nucleus tractus solitarius of the rat. These relationships could constitute an anatomical substrate for the presumed role of GABA in modulation of baroreceptor reflexes at this level.

Adrenergic Fibers↗
PubMed1995

The electric lobes of the electric ray (Torpedo marmorata) are innervated by GABAergic fibres: immunocytochemical evidence for dual innervation of electromotoneurons.

It is currently thought that the electric lobes of electric rays are innervated by a single neuronal system, the oval nucleus system. In the work reported here, the innervation of the electric lobes was studied with silver staining methods, acetylcholinesterase histochemistry and gamma-aminobutyric acid (GABA) immunocytochemistry. Two types of axon were observed in the lobes: thick GABA-immunonegative fibres, which originated from the oval nucleus, and thin GABAergic fibres of unknown origin, here reported for the first time. Electromotoneurons were strongly acetylcholinesterase-positive. Non-GABAergic and non-cholinergic neurons were observed in the oval nucleus, which is innervated by GABA-immunoreactive fibres. These results suggest that GABA may modulate electric discharge both directly, by GABAergic fibres that project to the lobes, and indirectly, by GABAergic fibres that project to the oval nucleus.

Acetylcholinesterase↗
PubMed1996

Pharmacological modifications of dopamine transmission do not influence the striatal in vivo binding of [3H]mazindol or [3H]cocaine in mice.

We have considered the in vivo striatal binding of two ligands of the neuronal dopamine uptake complex: [3H]cocaine and [3H]mazindol. The [3H]cocaine tracer dose labelled the dopamine uptake complex in striatum but not the noradrenaline complex in cerebellum. On the contrary, the [3H]mazindol tracer dose induced a marked labelling of the noradrenaline uptake complex in cerebellum; its prevention by desipramine (5 mg/kg) increased simultaneously the cerebral bioavailability and thereby the striatal labelling of the dopamine transporter. In mice submitted to treatments modifying dopaminergic transmission either to decrease it (gammabutyrolactone, 750 mg/kg, i.p.) or to increase it (L-DOPA, 200 mg/kg, i.p., dexamphetamine, 4 mg/kg, s.c., or their combination), only dexamphetamine pretreatment significantly reduced [3H]cocaine and [3H]mazindol binding. Thus it appears that the level of dopamine transmission would not interfere with the in vivo quantification of striatal dopamine uptake sites assessed with either ligands.

4-Butyrolactone↗
PubMed1996

Diazepam increases melatonin secretion of photosensitive pineal organs of trout in the photopic and mesopic range of illumination.

The pineal organ of teleost fish receives photic information directly through specialized photoreceptor cells that transmit their light response to second-order neurons and respond also with an endocrine light-dependent melatonin signal. In the present study we have analyzed the action of diazepam, a full agonist of the benzodiazepine receptor, on the photic regulation of the endocrine melatonin response of cultured trout pineal organs. Melatonin release of explanted pineal organs was clearly dependent on the irradiance of incident light with a maximum change during mesopic illuminations. Addition of diazepam to the superfusion medium significantly increased melatonin production in the mesopic and partly in the photopic range of illumination, without showing clear effects in the dark-adapted organ. Flumazenil, a central acting benzodiazepine antagonist, slightly reduced melatonin secretion. The action of diazepam appears to be comparable to a dark-pulse in the mesopic range of illuminations.

Animals↗
PubMed1996

Hypnotic and hypothermic effects of melatonin on daytime sleep in humans: lack of antagonism by flumazenil.

In this double-blind, placebo-controlled study we investigated whether 10 mg flumazenil, a pure benzodiazepine antagonist, can block the hypnotic and hypothermic effects of 3 mg melatonin. The design comprised four 7-h (1200-1900 h) testing periods, preceded by a 'no-treatment' adaptation period of the "7/13' sleep-wake paradigm. Six young healthy adult males were paid to participate. During each experimental period, tablets were administered at 1145 h (flumazenil or placebo) and at 1200 h (melatonin or placebo) in a randomized, double-blind, partially repeated Latin square design. Polysomnographic recordings and core body temperature recordings revealed that melatonin, either in combination with placebo or with flumazenil, significantly increased the amounts of sleep, and decreased core body temperature in comparison with placebo alone or the combination of flumazenil plus placebo. These results do not support the hypothesis that melatonin exerts its hypothermic and hypnotic effects via the central benzodiazepine receptors.

Adult↗
PubMed1985

The effect of peripherally administered GABA on noradrenaline-induced reflex vagal bradycardia in urethane anaesthetized rats.

Intravenously administered GABA significantly reduced the size of noradrenaline-induced reflex vagal bradycardia without affecting blood pressure increase. Intravenously administered GABA reduced bradycardia elicited by stimulation of preganglionic fibres in the vagus nerve. These findings provide evidence suggesting that, in addition to its well known effects on structures regulation cardiovascular function at CNS level GABA could modulate baroreceptor reflex(es) by acting at a peripheral site.

Anesthesia↗
PubMed1995

Pentobarbital differentially inhibits N-methyl-D-aspartate and kainate-stimulated [3H]noradrenaline overflow in rat cortical slices.

1. This study examined the ability of pentobarbital to inhibit NMDA and kainate-stimulated [3H]noradrenaline ([3H]NA) overflow in rat brain cortical slices. 2. Pentobarbital inhibited NMDA-evoked [3H]NA overflow at 100 microM and greater and inhibited kainate-evoked [3H]NA overflow at 10 microM and greater. 3. The ability of pentobarbital to inhibit concentration-response curves for NMDA and kainate-evoked overflow of [3H]NA were also examined. Pentobarbital (300 microM) caused a 20% reduction in NMDA and a 50% reduction in kainate-induced maximal responses.

Adrenergic alpha-Agonists↗
PubMed1995

Diazepam decreases the response to the electrical stimulation of the nerve-skin preparation of the toad Caudiverbera caudiverbera.

1. The effect of diazepam was examined in the nerve skin preparation of the toad Caudiverbera caudiverbera. 2. Nerve stimulation was followed immediately by a transient increase in short-circuit current (SCC) and in the potential difference (PD), which consisted of a rapid and then a slow component. 3. Diazepam concentrations from 5.0 x 10(-5)M to 5.1 x 10(-4)M caused a dose-dependent block of both components to a 30% of their control values and also reduced the stimulatory responses to noradrenaline in this preparation. 4. Diazepam antagonized the potassium blocking effect of barium. 5. These results, based on electrophysiological and pharmacological evidence, are consistent with a calcium and sodium blocking effect of diazepam on the nerve skin junction of C. caudiverbera.

Adrenergic alpha-Agonists↗
PubMed1987

Modulation of cerebellar granule cell activity by iontophoretic application of serotonergic agents.

Serotonergic fibers have been identified within the granule cell layer of the cerebellar cortex; however, their functional significance has not been identified. In this study the effect of serotonin on granule cell spontaneous activity was determined in the rat cerebellum. Of the 136 granule cells tested, 44.8% displayed a decrease in firing rate, 21.3% increased firing rate and 33.8% were not affected. The serotonin-induced changes in activity were not blocked by bicuculline or methysergide. The serotonin agonist 1,3 (trifluoromethylphenyl) piperazine mimicked the serotonin-induced suppressive response. Iontophoretically applied serotonin was also found to modulate GABA-induced suppression of granule cell activity. The variable effects of serotonin on spontaneous activity suggests the presence of more than one type of serotonergic receptor in the cerebellar granule cell layer.

Animals↗
PubMed1996

Effects of GABA uptake inhibitors on posthypoxic myoclonus in rats.

Male Sprague-Dawley rats developed posthypoxic myoclonus following 10-min cardiac arrest and resuscitation. Previous results showed that dysfunction of central GABAergic neurotransmission may contribute to the disease. In current studies, effects of GABA uptake inhibitors, guvacine hydrochloride (1,2,5,6-tetrahydro-3-pyridine carboxylic acid hydrochloride) and (+/-)-cis-4-hydroxynipecotic acid ([+/-]-cis-4-hydroxy-3-piperidine carboxylic acid), in the pathophysiology of posthypoxic myoclonus were investigated. Administration of guvacine (1 or 10 mg/kg, IP) or nipecotic acid (0.5 or 5 mg/kg, IP) significantly attenuated myoclonus scores of the animals. Tolerance to antimyoclonus effects of these two compounds did not develop after chronic administration (twice a day for 14 days) of guvacine (10 mg/kg, IP) or nipecotic acid (5 mg/kg, IP). On the other hand, tolerance was noticed with clonazepam (2.5 mg/kg, IP twice a day for 7 days). The results indicate that guvacine or nipecotic acid may be used in combination with (at reduced doses) or as alternatives to clonazepam to treat patients with the disease so as to reduce tolerance phenomenon usually associated with clonazepam.

Animals↗
PubMedDate not supplied

Drug effects on response-duration differentiation. IV: Effects of trimethyltin.

Trimethyltin (TMT) is a toxicological agent that produces damage in a number of limbic structures, resulting in concomitant disruptions of behavior. The purpose of the present study was to determine the utility of response-duration differentiation (RDD) responding as a behavioral baseline for studying the behavioral consequences of TMT administration. Under the RDD schedule, responses of a restricted duration (1-1.3 s) were reinforced, and disruption of this performance may represent effects upon fine motor control, timing behavior, or both. Two doses of TMT (4 mg/kg) were administered 1 week apart, and behavior under the schedule was studied daily for 6 weeks thereafter in a group of four rats. Additionally, the effects of diazepam (0.1-3mg/kg) administered prior to and following TMT administration were compared. TMT produced disruptions in accuracy of responding and increases in rates of responding in the weeks following its administration. Behavior had generally recovered by 6 weeks after the first TMT administration. Diazepam flattened the relative frequency distributions of response durations at lower doses in the TMT-treated rat. These data show that RDD responding is sensitive to the effects of TMT, and TMT treatment can result in alterations in the effects of diazepam.

Animals↗
PubMed1996

Anxiolytic activity of intraventricularly administered atrial natriuretic peptide in the rat.

Rat atrial natriuretic peptide (ANP) was investigated for putative anxiolytic activity in rats, following intracerebroventricular (ICV) administration. ANP in doses of 200 and 500 ng/rat induced significant anxiolysis, comparable with that of lorazepam (0.5 mg/kg, i.p.) in a variety of anxiety models (open-field, elevated plus-maze, social interaction, and novelty-induced feeding suppression tests). Isatin, an endogenous anxiogenic indole, shown to be an antagonist of ANP in vitro, significantly inhibited the anxiolytic effect of ANP in the elevated plus-maze test in subanxiogenic doses. The anxiolytic action of ANP was unaffected by flumazenil, a benzodiazepine receptor antagonist. Conversely, the anxiolytic action of lorazepam was antagonized by flumazenil but not by isatin. The data indicate that ANP may function as an endogenous anxiomodulator, which may act in conjunction with isatin independently of benzodiazepine receptors. These results strengthen the evidence for links between physiological systems involved in anxiety and those in natriuresis.

Animals↗