Gamma-aminobutryic Acid Research Articles

Functional Topography and Development of Inhibitory Reticulothalamic Barreloid Projections.

The thalamic reticular nucleus (TRN) is the main source of inhibition to the somatosensory thalamus (ventrobasal nucleus, VB) in mice. However, the functional topography and development of these projections with respect to the VB barreloids has been largely unexplored. In this respect, to assist in the study of these projections, we have utilized a vesicular gamma-aminobutryic acid (GABA) transporter (VGAT)-Venus transgenic mouse line to develop a brain slice preparation that enables the rapid identification of inhibitory neurons and projections. We demonstrate the utility of our in vitro brain slice preparation for physiologically mapping inhibitory reticulothalamic (RT) topography, using laser-scanning photostimulation via glutamate uncaging. Furthermore, we utilized this slice preparation to compare the development of excitatory and inhibitory projections to VB. We found that excitatory projections to the barreloids, created by ascending projections from the brain stem, develop by postnatal day 2–3 (P2–P3). By contrast, inhibitory projections to the barreloids lag ~5 days behind excitatory projections to the barreloids, developing by P7–P8. We probed this lag in inhibitory projection development through early postnatal whisker lesions. We found that in whisker-lesioned animals, the development of inhibitory projections to the barreloids closed by P4, in register with that of the excitatory projections to the barreloids. Our findings demonstrate both developmental and topographic organizational features of the RT projection to the VB barreloids, whose mechanisms can now be further examined utilizing the VGAT-Venus mouse slice preparation that we have characterized.

Suppression of underlying neuronal fluctuations mediates EEG slowing during general anaesthesia

The physiological mechanisms by which anaesthetic drugs modulate oscillatory brain activity remain poorly understood. Combining human data, mathematical and computational analysis of both spiking and mean-field models, we investigated the spectral dynamics of encephalographic (EEG) beta-alpha oscillations, observed in human patients undergoing general anaesthesia. The effect of anaesthetics can be modelled as a reduction of neural fluctuation intensity, and/or an increase in inhibitory synaptic gain in the thalamo-cortical circuit. Unlike previous work, which suggested the primary importance of gamma-amino-butryic-acid (GABA) augmentation in causing a shift to low EEG frequencies, our analysis demonstrates that a non-linear transition, triggered by a simple decrease in neural fluctuation intensity, is sufficient to explain the clinically-observed appearance – and subsequent slowing – of the beta-alpha narrowband EEG peak. In our model, increased synaptic inhibition alone, did not correlate with the clinically-observed encephalographic spectral changes, but did cause the anaesthetic-induced decrease in neuronal firing rate. Taken together, our results show that such a non-linear transition results in functional fragmentation of cortical and thalamic populations; highly correlated intra-population dynamics triggered by anaesthesia decouple and isolate neural populations. Our results are able to parsimoniously unify and replicate the observed anaesthetic effects on both the EEG spectra and inter-regional connectivity, and further highlight the importance of neural activity fluctuations in the genesis of altered brain states.

Dorsolateral Prefrontal Cortex GABA Concentration in Humans Predicts Working Memory Load Processing Capacity.

This study demonstrated for the first time that the amount of gamma-aminobutryic acid (GABA), the major inhibitory neurotransmitter of the brain, in an individual's prefrontal cortex predicts working memory (WM) task performance. Given that WM is required for many of the most characteristic cognitive and behavioral capabilities in humans, this finding could have a significant impact on our understanding of the neural basis of complex human behavior. Furthermore, this finding suggests that efforts to preserve or increase brain GABA levels could be fruitful in remediating WM-related deficits associated with neuropsychiatric conditions.

Bioaktivitas Minyak Atsiri Daun Bandotan (Ageratum conyzoides) Terhadap Respon Fisiologis (Glukosa Darah Dan Tachiventilasi) Ikan Koi (Cyprinus carpio) <Br><I>[Bioactivity Essential Oil Of Bandotan Leaf (Ageratum conyzoides) On Koi (Cyprinus carpio) Physiological Responses (Blood Glucose And Tachiventilation) ]<I>

Abstract Koi (C. carpio) is one of famous ornamental fish in Indonesia. Fish often be subject of change or stessor like physical, chemical and biology on culture. Stress in fish caused released cortisol hormone and cathecolamine hormone. Cathecolamine increase glicogenolisis, cardiovascular regulation and respiration fungtion. Blood glucose and tachiventilation (opercular movement) can indicate stress respon in fish. Essential oil of A. conyzoides have central analgesic activity. Analgesic drugs in vertebrae can reduce stress in fish. Essential oil shown inhibitory effect of GABA transminase, an enzime GABA (gammaaminobutryic acid) degradation which can provoking sedation. Sedation effect in fish reduce blood glucose and tachiventilation. Potency bioactive essential oil of bandotan leaf compound haven’t been know in aquaculture. The potency based of LC50 (Lethal Consentration 50 %) value Purpose of this research determined effect of essential oil Ageratum conyzoides leaf on Koi (Cyprinus carpio) Phsycology Response (Blood Glucose and Tachiventilation) every 4 hours durung 24 hours and LC50-24 hours. Research was conducted at Laboratory of Faculty of Fisheries and Marine Airlangga University Surabaya. Research design used Completely Randomized Design and followed by Duncan's Multiple range test. Results of analysis of variance (ANAVA) from early observation and every 4 hours during 24 hours day showed that each treatment of essential oil Ageratum conyzoides leaf gave a significantly different effect on the blood glucose and tachiventilation (P <0.05). The highest average of blood glucose was found in D treatment at second observation (443,67 mg/dl) and the lowest was found in C treatment (60,67 mg/dl). The highest average of tachiventilation was found in D treatment at first observation (1730 bit/9 minute) and the lowest was found in A treatment (437,67 bit/9 minute) at early observation. LC50-24 hours essenial oil Ageratum conyzoides leaf is 34,047 ppm. Based on measurements of water quality, treatments was still viable and good to supported viability of Cyprinus carpio during research, water temperature range between 29-31oC, range of dissolved oxigen 4-6 mg/l, pH ranges 7,5-8,3 and 0,0060,27 mg/l on ammonia.

Lactational Anovulation in Mice Results From a Selective Loss of Kisspeptin Input to GnRH Neurons

In mammals, lactation is associated with a period of infertility characterized by the loss of pulsatile secretion of GnRH and cessation of ovulatory cycles. Despite the importance of lactational infertility in determining overall fecundity of a species, the mechanisms by which the suckling stimulus suppresses GnRH secretion remain unclear. Because kisspeptin neurons are critical for fertility, the aim of this study was to test the hypothesis that reduced kisspeptin expression might mediate the lactation-induced suppression of fertility, using mouse models. In the rostral periventricular area of the third ventricle (RP3V), a progressive decrease in RP3V Kiss1 mRNA levels was observed during pregnancy culminating in a 10-fold reduction during lactation compared with diestrous controls. This was associated with approximately 60% reduction in the numbers of kisspeptin-immunoreactive neurons in the RP3V detected during lactation. Similarly, in the arcuate nucleus there was also a significant decrease in Kiss1 mRNA levels during late pregnancy and midlactation, and a notable decrease in kisspeptin fiber density during lactation. The functional characteristics of the RP3V kisspeptin input to GnRH neurons were assessed using electrophysiological approaches in an acute brain slice preparation. Although endogenous RP3V kisspeptin neurons were found to activate GnRH neurons in diestrous mice, this was never observed during lactation. This did not result from an absence of kisspeptin receptors because GnRH neurons responded normally to 100 nM exogenous kisspeptin during lactation. The kisspeptin deficit in lactating mice was selective, because GnRH neurons responded normally to RP3V gamma aminobutryic acid inputs during lactation. These data demonstrate that a selective loss of RP3V kisspeptin inputs to GnRH neurons during lactation is the likely mechanism causing lactational anovulation in the mouse.

The use of zolpidem in the treatment of progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a debilitating progressive neurodegenerative disorder for which there is no proven pharmacological treatment. Zolpidem immediate release formulation has been reported to show short-term improvements in motor function and voluntary saccadic eye movements, but the benefits were not sustained. A 61-year-old man with a 4-year history of PSP was observed over 6 months to have sustained improvement in motor function, pseudobulbar symptoms and ocular motility 2 months after commencing zolpidem controlled release (CR) formulation. He was admitted to hospital and a detailed neurological and functional assessment recorded on video after withdrawal of zolpidem CR, and again following re-introduction of the medication. Within 1 hour of administration of 25 mg zolpidem CR the patient had a dramatic improvement in fine motor skills, dexterity, speed and fluidity of movement, facial and vocal expression, oropharyngeal coordination and function and pursuit, and voluntary saccadic eye movements. These improvements were observed for 4 hours to 5 hours post-dose and were reproducible on subsequent withdrawal and re-challenging. We found that zolpidem CR, a gamma aminobutryic acid (GABA)ergic agonist of the benzodiazepine type 1 receptor, caused sustained improvement in motor and ocular symptoms in a patient with PSP over 6 months. Further studies are needed to determine the potential roles of GABA neurotransmission in PSP.

Phase I clinical trial of MLN8054, a selective inhibitor of Aurora A kinase

3577 Background: MLN8054 is a small molecule inhibitor of Aurora A kinase, with > 150-fold greater potency against this enzyme than the structurally related but functionally distinct Aurora B kinase. Because of its structural similarity to benzodiazepines, MLN8054 binds to the gamma-aminobutryic acid alpha 1 benzodiazepine (GABAA a1 BZD) receptor and in preclinical studies caused benzodiazepine-like CNS effects. Methods: MLN8054 was given as capsule by mouth for 7 consecutive days, repeated every 21 days. Cohorts of 3- 6 patients (pts) were enrolled to successively increasing doses until dose-limiting toxicity was seen in = 2 pts at a given dose level. Serial blood samples were collected to estimate PK; skin biopsies were obtained before and 6 hours after the first dose to assess inhibition of Aurora A kinase in basal epithelial cells. Results: 22 pts were enrolled to evaluate single daily doses of 5, 10, 20, 30 and 40 mg/day. MLN8054 was in general rapidly absorbed, displayed dose-proportionate exposure, and had a mean elimination half-life of 35 hours. The ratio of peak to trough plasma concentrations was approximately 5. Reversible grade 2 somnolence was first seen in 3 patients treated at 20 mg/day, and 2/4 patients treated at 40 mg/day experienced reversible grade 3 somnolence. In order to reduce the sedative effects of MLN8054, 16 additional pts were enrolled to doses of 25, 35, 45 and 55 mg/day given as divided doses on a QID schedule. Two of 4 pts treated at the 55 mg/day dose experienced reversible grade 3 somnolence, establishing 45 mg/day as the maximum tolerated total daily dose on a QID schedule. No myelosuppression or mucosal toxicity was seen at any dose with either schedule. Immunohistochemical analysis of skin biopsies from pts treated with once daily dosing did not demonstrate accumulation of cells in mitosis. Three pts with metastatic colorectal cancer treated with single daily doses of MLN8054 received = 8 cycles of treatment. Conclusions: The study is now escalating divided daily dosing of MLN8054 with the co-administration of methylphenidate. Post-treatment skin biopsies are now obtained on Day 7. Duration of treatment will be extended to 14 days, since steady-state concentrations of MLN8054 require 5–7 days of dosing, and because the effects of Aurora A kinase inhibition are duration-dependent. No significant financial relationships to disclose.

Existence and Theoretical Aspects of Homomeric and Heteromeric Dopamine Receptor Complexes and Their Relevance for Neurological Diseases

Dopamine (DA) and other receptors physically interact in the plasma membrane of basal ganglia neurons forming receptor mosaics (RMs). Two types of RMs are discussed, homomers formed only by DA-receptor (DA-R) subtypes and heteromers formed by DA-R associated with other receptors, such as A2A, A1, mGluR5, N-methyl-D-aspartate (NMDA), gamma-aminobutryic acid (GABA)-A, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. By being part of horizontal molecular networks, RMs tune multiple effector systems already at membrane level, such as G protein regulated inward rectifying potassium channels and dopamine transporter activity. Also, ligand-gated ion channels such as GABA-A and NMDA receptors are modulated by DA-R, e.g., in the striatal GABA output neurons through the formation of heteromeric complexes with these receptors. Thus, intramembrane DA-R-receptor interactions play an important role in the information handling in the basal ganglia. On this basis, functional implications of DA RM in physiological and pathological conditions are discussed. The effects of temperature on RM are discussed not only because receptor-decoding mechanisms are temperature sensitive, but also in view of the suggestion that possible ordering effects (i.e., changes in the entropy of a receptor complex) induced by a ligand are as a result of alterations in the receptor oligomerization (i.e., are related to rearrangements of the RM). Hence, brain temperature may have profound effects on brain integrative functions not only because its effects on the kinetics of biochemical reactions, but also for its effects on receptor geometry, building up of RM, and alterations in protein expression, as is the case of H-channels following febrile seizures.

Sleep oscillations developing into seizures in corticothalamic systems.

The aim of this article is to discuss the neuronal substrates of sleep oscillations leading to seizures consisting of spike-wave (SW) complexes at 2-4 Hz, mimicking those seen in absence epilepsy, or SW and polyspike-wave (PSW) complexes at 1.5-2.5 Hz, often associated with fast runs at 10-15 Hz, as in the Lennox-Gastaut syndrome. Extracellular recordings were done in permanently implanted animals during the natural waking-sleep cycle. Single and dual simultaneous recordings from cortical neurons, cortical and thalamic neurons, or cortical neurons and glial cells were performed in cats under ketamine-xylazine anesthesia. (a) The minimal substrate of SW seizures is the neocortex because such seizures may occur in thalamectomized animals, in which spindles are absent. In intact-brain animals, SW seizures are initiated in neocortex and spread to the thalamus after a few seconds. The majority of thalamocortical (TC) neurons are steadily hyperpolarized throughout the cortical SW seizures. (b) In the Lennox-Gastaut syndrome, the paroxysmal depolarizing shifts (PDSs) associated with the EEG "spike" of SW/PSW complexes contain an important inhibitory component, whereas the hyperpolarization during the EEG "wave" component is not due to gamma-aminobutryic acid (GABA)ergic inhibitory postsynaptic potentials (IPSPs) but is ascribed to a mixture of disfacilitation and K+ currents. As is also the case with seizures consisting of pure SW complexes, the majority of TC neurons are hyperpolarized during the cortical paroxysms and disinhibited after the cessation of cortical seizures. Seizures with SW complexes and of the Lennox-Gastaut type preferentially evolve from sleep oscillations. They are initiated in neocortex and spread to the thalamus after a few seconds. The majority of TC neurons are inhibited during these seizures.

Don't ask, don't tell, but benzodiazepines are still the leading treatments for anxiety disorder.

Article AbstractModern guidelines for psychopharmacologic treatment of anxiety disorders have evolved from recommending GABAergic (gammaaminobutryic acid) benzodiazepines to recommending serotonergic agents for first-line use. This trend, along with adverse publicity about the dependence potential of benzodiazepines, might lead one to suspect that benzodiazepines, once prominent in the 1980s but now generic and often disparaged, must have significantly declined in use. Not so. In fact, benzodiazepines are still more widely prescribed than antidepressants for the treatment of anxiety disorders (Table 1), and alprazolam is the single most commonly prescribed agent for mood and anxiety disorders(Table 2).

Evidence for the segregation of a major gene for human plasma GABA levels.

Gamma-aminobutryic acid (GABA) is a major neurotransmitter in the central nervous system, and plasma levels of GABA may reflect brain GABA activity. In 35-40% of patients with mood disorders, plasma GABA levels are low compared to psychiatrically normal controls. Low plasma GABA in this subgroup of patients has characteristics of a biological trait marker for mood disorders. Low plasma GABA is also found in a subset of patients with alcohol dependence, but not in schizophrenia, anxiety, or eating disorders, suggesting some diagnostic specificity. Previous data from a small study of monozygotic twins are consistent with the hypothesis that plasma GABA levels are under genetic control. To better understand these mechanisms, we conducted a segregation analysis of plasma GABA levels in a sample of 157 individuals from 50 nuclear families. Analysis using the Class D regressive model indicated that the familial transmission of plasma GABA levels is compatible with the segregation of a recessive major gene. Our results suggest that plasma GABA levels are under single gene control. Future research should address the precise mechanisms which may account for the abnormality in GABA levels seen in a subset of patients with mood disorders.

Physiology of the aged Fischer 344 rat inferior colliculus: responses to contralateral monaural stimuli

1. Presbycusis, age-related hearing loss, is an ever increasing problem in our aging society. It involves changes in both the peripheral and central portions of the auditory system. The inferior colliculus (IC) has been shown to display age-related changes including decreased gamma-aminobutryic acid (GABA) levels, decreased glutamate decarboxylase levels, and decreased binding by GABAB receptors, as well as rearrangement of axon terminals in aging Fischer 344 (F344) rats. Age-related physiological changes have also been noted in the ICs of C57 and CBA mice. 2. Given the age-related alterations in the inhibitory neurotransmitter system, we hypothesized that aged F344 rats would show alterations in the physiological response properties of their IC neurons due to an imbalance in the relative levels of inhibition and excitation affecting the neuronal firing. 3. In vivo extracellular single-unit recordings were made from 297 IC neurons in ketamine/xylazine-anesthetized aged (24 mo) F344 rats. Locations of recorded units were determined from the electrode track marks and horseradish peroxidase marks. Results were compared with those obtained from young adult (3 mo) animals. 4. Average threshold increased from 25.4 dB SPL in young rats to 56.1 dB SPL in aged rats. 5. Although there was a reduction in the percentage of units recorded at either extreme of the frequency range in aged animals, the characteristic frequency (CF) range and mean did not differ between the two groups. 6. For the IC as a whole, no differences were noted in spontaneous activity, first spike latency, dynamic range, percentage of units with nonmonotonic contralateral CF tone rate/intensity functions (RIFs), or percentage of units sensitive to change in CF tone presentation rate. 7. In aged rats, a higher percentage of units was poorly responsive to auditory stimulation. 8. In the aged rat, there was a 12% reduction in the maximum discharge rate, a 12% increase in the percentage of units classified as onset in their temporal response pattern, and an 18% increase in the breadth of the isointensity functions at 30 dB above threshold. 9. Age-related changes in the central nucleus of the IC (CIC) frequently differed from those observed in the external cortex of the IC (ECIC). The percentage of units classified as having nonmonotonic contralateral tone RIFs decreased with age in the CIC but increased with age in the ECIC, and the percentage of units classified as onset in their temporal response pattern increased with age in the CIC but did not change with age in the ECIC. 10. The results of this study support the hypothesis that there is an age-related shift to higher intensities in the working range of most CIC units along with a small, selective deficit in inhibitory processing. When considered in conjunction with the mouse aging studies conducted by other researchers and with the results of a similar study of single units in the visual system (lateral geniculate nucleus) of young and aged rhesus monkeys, these results suggest that compensatory mechanisms are highly active in sensory systems as animals age. Despite deficits that lead to reduced input to the IC and neurochemical changes affecting neurotransmitter levels, IC neurons in aged rats are able to respond to most simple auditory stimuli in a fashion quite similar to that observed in young rats.

Mechanisms of action of antiepileptic drugs

Depending on their mechanism of action, anticonvulsant drugs in clinical use may be divided into three groups: those drugs which facilitate gamma-aminobutryic acid (GABA)ergic neurotransmission; those which block neuronal ion channels; and those whose mechanism of action is unresolved. The compounds acting on GABAergic systems may be further subdivided into those which modulate transmission through chloride channels, e.g. the barbiturates and the benzodiazepines; those compounds, in particular vigabatrin, which reduce the degradation of GABA by blocking GABA transaminase; and those which inhibit the re-uptake of GABA into the presynaptic terminal. The other group of compounds whose mechanism of action is known are those which block neuronal ion channels. Blockage of voltage-operated sodium channels by lamotrigine, phenytoin or carbamazepine leads to decreased electrical activity and, probably, a subsequent reduction in glutamate release. Conversely, ethosuximide, blocks voltage-operated calcium channels, especially those which mediate calcium currents in thalamic neurones. Of those drugs in which the mechanism of action is unknown, sodium valproate is the prime example. An antagonistic action at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor might also be a possibility, which could be the case with some of the newer compounds currently undergoing evaluation.

Cellular distribution of L-glutamate decarboxylase (GAD) and gamma-aminobutyric acidA (GABAA) receptor mRNAs in the retina.

1. Gamma-aminobutryic acid (GABA), a major inhibitory transmitter of the vertebrate retina, is synthesized from glutamate by L-glutamate decarboxylase (GAD) and mediates neuronal inhibition at GABAA receptors. GAD consists of two distinct molecular forms, GAD65 and GAD67, which have similar distribution patterns in the nervous system (Feldblum et al., 1990; Erlander and Tobin, 1991). GABAA receptors are composed of several distinct polypeptide subunits, of which the GABAA alpha 1 variant has a particularly extensive and widespread distribution in the nervous system. The aim of this study was to determine the cellular localization patterns of GAD and GABAA alpha 1 receptor mRNAs to define GABA- and GABAA receptor-synthesizing neurons in the rat retina. 2. GAD and GABAA alpha 1 mRNAs were localized in retinal neurons by in situ hybridization histochemistry with 35S-labeled antisense RNA probes complementary to GAD67 and GABAA alpha 1 mRNAs. 3. The majority of neurons expressing GAD67 mRNA is located in the proximal inner nuclear layer (INL) and ganglion cell layer (GCL). Occasional GAD67 mRNA-containing neurons are present in the inner plexiform layer. Labeled neurons are not found in the distal INL or in the outer nuclear layer (ONL). 4. GABAA alpha 1 mRNA is expressed by neurons distributed to all regions of the INL. Some discretely labeled cells are present in the GCL. Labeled cells are not observed in the ONL. 5. The distribution of GAD67 mRNA demonstrates that numerous amacrine cells (conventional, interstitial, and displaced) and perhaps interplexiform cells synthesize GABA. These cells are likely to employ GABA as a neurotransmitter. 6. The distribution of GABAA alpha 1 mRNA indicates that bipolar, amacrine, and perhaps ganglion cells express GABAA receptors having an alpha 1 polypeptide subunit, suggesting that GABA acts directly upon these cells.

Canine GM2Gangliosidosis: Morphological and Biochemical Analysis

Beta-hexosaminidase activity and the effects of ganglioside storage on neuronal function were examined in a German shorthair pointer (GSHP) with progressive neurodegenerative signs. Morphologic evidence of neuronal storage and massive accumulation of GM2 ganglioside were present. Beta-hexosaminidase activity in plasma, liver, kidney, and brain, assayed with use of unsulfated fluorogenic substrates, was normal. There was no pathologic accumulation or aberrant localization of phosphorylated neurofilaments in neurons. Activity of cortical neurotransmitter synthesizing enzymes, choline acetyltransferase, and glutamate decarboxylase was unaffected. Ligand binding to carrier sites for choline high affinity uptake identified with [3H]hemicholinium-3 was increased, whereas post-synaptic binding to muscarinic cholinergic ([3H]QNB) and gamma-aminobutyric acid receptors ([3H]muscimol) was reduced.

Deuterium isotope effect in gamma-aminobutyric acid transamination: determination of rate-limiting step.

The rate of transamination of gamma-aminobutryic acid (GABA) catalyzed by hog brain gamma-aminobutyrate aminotransferase was substantially reduced when the hydrogen at the gamma-carbon position was replaced by deuterium. The deuterium isotope effect of this reaction has been substantiated by fluorometric, radiometric, and mass spectrometric procedures and assessed kinetically. The ratios of Vmax of the nonlabeled substrate/Vmax of the deuterated substrate obtained under different conditions ranged from 6 to 7. This indicates that the cleavage of the hydrogen from the gamma-carbon is the rate-determining step in GABA transamination. Similar isotope effects have also been shown to occur in the peripheral system in vivo.

Messenger RNA from bovine retina induces kainate and glycine receptors in Xenopus oocytes.

The retina contains several types of nerve cells that communicate through chemical synapses. The transmitter and receptor molecules that mediate signal transmission across these synapses need further characterization. For this purpose, poly (A)+ mRNA was isolated from bovine retinas and injected into Xenopus laevis oocytes. Translation of the foreign mRNA induced the oocyte membrane to acquire functional receptors to kainate and, to a lesser extent, also receptors to glycine, gamma-aminobutryic acid (GABA), aspartate and glutamate. Thus, the cells in the retina must contain different messengers coding for these neurotransmitter receptors. Activation of the kainate receptors opens membrane channels, generating an ionic current which has an equilibrium potential close to 0 mv. The current is well maintained during prolonged application of kainate, and hence these receptors may be involved in the neurotoxic effects produced by kainate in the retina.

Amino-oxyacetic acid: Effects on multiple fixed ratio-fixed interval performance in the rat

Disruptions in multiple FI-FR operant performance as a function of administration of amino-oxyacetic acid, a drug which increases brain levels of gamma-aminobutryic acid, were studied. The drug caused profound disruptions in response rate and temporal patterning, but these effects were not temporally correlated with the time-course of neurochemical effects reported by other investigators.