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The Journal of Pharmacy and Pharmacology May 1979Contralateral turning behaviour following unilateral intranigral injection of a large series of GABA analogues was investigated. The results indicated that the turning...
Contralateral turning behaviour following unilateral intranigral injection of a large series of GABA analogues was investigated. The results indicated that the turning behaviour was induced stereospecifically and was selectively antagonized by the GABA antagonist bicuculline methochloride. The comparative potencies of a series of GABA agonists related to muscimol in general corresponded well to the affinity for 3H-GABA receptor sites and to the depressant action on single neurons using microelectrophoretic administration. However, the GABA agonists trans-aminocrotonic acid and 3-aminopropanesulphonic acid were much weaker than expected from in vitro studies. The GABA-uptake inhibitors nipecotic acid and guvacine showed only weak and short-lasting effects. The GABA-transaminase inhibitor gamma-acetylenic GABA showed delayed effects compared with the agonists which acted immediately. It is proposed that this behavioural effect may be a sensitive and quantitative method for evaluation of GABA agonists in vivo.
Topics: Animals; Humans; Injections; Male; Muscimol; Oxazoles; Rats; Receptors, Drug; Stereotyped Behavior; Substantia Nigra; Time Factors; gamma-Aminobutyric Acid
PubMed: 37300
DOI: 10.1111/j.2042-7158.1979.tb13506.x -
Investigative Ophthalmology & Visual... Dec 1980Gamma-aminobutyric acid (GABA) is a candidate as a neurotransmitter in the vertebrate retina. The GABA analogue muscimol has been used to probe the properties of GABA...
Gamma-aminobutyric acid (GABA) is a candidate as a neurotransmitter in the vertebrate retina. The GABA analogue muscimol has been used to probe the properties of GABA receptors in other parts of the vertebrate central nervous system (CNS). We thus used 3H-muscimol to investigate potential GABA receptors in the retinas of goldfish and chick by means of biochemical assay techniques and light microscopic autoradiography. In both animals 3H-muscimol shows specific and saturable binding with a dissociation constant (KD) of about 10 nM. GABA effectively inhibits 3H-muscimol binding at 50% inhibitory concentration (IC50) of 10(-6) M. The labeling pattern of 7 x 10(-7) M 3H-muscimol shows common features for both species in that amacrine cell bodies are intensely labeled, horizontal cells are much less so, and there is a laminar pattern throughout the inner plexiform layer (IPL). A 1 mM concentration of GABA abolishes 3H-muscimol labeling in the chick retina and throughout much of the goldfish retina except for some label over amacrine cells and the distal two thirds of the IPL. The intense somatic labeling suggests neuronal uptake of 3H-muscimol, and indeed, virtually all 3H-muscimol labeling is abolished with the addition of 0.4 mM ouabain. The uptake pattern of 3H-GABA differs from that of 3H-muscimol and is largely unaffected by the addition of 1 mM muscimol. We conclude that 3H-muscimol binding in retinas can be adequately demonstrated biochemically but that only 3H-muscimol uptake is observed with autoradiography from tissue conventionally processed through Epon. The fact that GABA can inhibit 3H-muscimol uptake whereas the reverse is not the case shows that the transport carriers for muscimol and GABA are different. Finally, the strong degree of 3H-muscimol uptake by retinal neurons raises serious questions about the use of 3H-muscimol as a probe for GABA synaptic receptors in the retina with autoradiography.
Topics: Animals; Autoradiography; Chickens; Goldfish; Muscimol; Neurons; Neurotransmitter Agents; Oxazoles; Receptors, Cell Surface; Receptors, GABA-A; Retina; gamma-Aminobutyric Acid
PubMed: 6108301
DOI: No ID Found -
Journal of Comparative Physiology. A,... Feb 1989The suprachiasmatic nucleus (SCN) of the hypothalamus contains a neural oscillatory system which regulates many circadian rhythms in mammals. Immunohistochemical...
The suprachiasmatic nucleus (SCN) of the hypothalamus contains a neural oscillatory system which regulates many circadian rhythms in mammals. Immunohistochemical evidence indicates that a relatively high density of GABAergic neurons exist in the suprachiasmatic region. Since intraperitoneal injections of the benzodiazepine, triazolam, have been shown to induce phase shifts in the free-running circadian rhythm of locomotor activity in the golden hamster, the extent to which microinjections of muscimol, a specific agonist for gamma-aminobutyric acid (GABA), may cause phase-shifts in hamster activity rhythms was investigated. Stereotaxically implanted guide cannulae aimed at the region of the SCN were used to deliver repeated microinjections in individual animals. A phase-response curve (PRC) generated from microinjections of muscimol revealed that the magnitude and direction of permanent phase-shifts in the activity rhythm were associated with the time of administration. The PRC generated for muscimol was characterized by maximal phase-advances induced 6 h before activity onset and by maximal phase-delays which occurred 6 h after activity onset. The PRC for muscimol had a shape similar to a PRC previously generated for the short-acting benzodiazepine, triazolam. Single microinjections of different doses of muscimol given 6 h before activity onset induced phase-advances in a dose-dependent fashion. Histological analysis revealed that phase shifts induced by the administration of muscimol were associated with the proximity of the injection site to the SCN area. These data indicate that a GABAergic system may exist within the suprachiasmatic region as part of a central biological clock responsible for the regulation of the circadian rhythm of locomotor activity in the golden hamster.
Topics: Animals; Circadian Rhythm; Cricetinae; Male; Mesocricetus; Motor Activity; Muscimol; Suprachiasmatic Nucleus
PubMed: 2657038
DOI: 10.1007/BF00616752 -
Life Sciences Jan 1987[3H]muscimol binding and glutamic acid decarboxylase (GAD) activity in the prefrontal cortex and caudate nucleus of autopsied brains from 19 chronic schizophrenics and...
[3H]muscimol binding and glutamic acid decarboxylase (GAD) activity in the prefrontal cortex and caudate nucleus of autopsied brains from 19 chronic schizophrenics and 17 control subjects were investigated. In the schizophrenics, saturation analysis with varying concentrations of [3H]muscimol revealed an increase in the number of GABAA receptors, but there was no significant difference in the affinity. In addition, the enhancement of [3H]muscimol binding by diazepam was significantly greater in schizophrenics than in controls. GAD activity did not differ between controls and schizophrenics. The possibility that GABAergic mechanisms might play a role in case of chronic schizophrenia should be given further attention.
Topics: Adult; Aged; Aged, 80 and over; Binding Sites; Brain Chemistry; Glutamate Decarboxylase; Humans; Middle Aged; Muscimol; Receptors, GABA-A; Schizophrenia
PubMed: 3025545
DOI: 10.1016/0024-3205(87)90341-9 -
Pharmacology, Biochemistry, and Behavior Aug 1987In male Sprague-Dawley rats acute ethanol (1.0 and 2.0 g/kg) produced impairment of motor coordination and induced hypnosis (4.0 g/kg). Muscimol (1.25 mg/kg, IP) prior...
In male Sprague-Dawley rats acute ethanol (1.0 and 2.0 g/kg) produced impairment of motor coordination and induced hypnosis (4.0 g/kg). Muscimol (1.25 mg/kg, IP) prior to ethanol administration enhanced motor impairment as measured by the aerial righting reflex. The rate of ethanol disappearance from the blood was unaltered by muscimol. Functional tolerance to the effect of ethanol on sleep time was produced by a 24 hr ethanol inhalation procedure. Animals tested 48 hr after ethanol inhalation exhibited a reduced sleep time from ethanol (4.0 g/kg). Muscimol (1.75 mg/kg) was administered along with ethanol 48 hr following 1 day of ethanol inhalation. Although the animals exhibited tolerance to ethanol-induced hypnosis, they did not manifest tolerance to the effect of muscimol.
Topics: Animals; Brain; Drug Interactions; Drug Tolerance; Ethanol; Male; Muscimol; Posture; Psychomotor Performance; Rats; Rats, Inbred Strains; Sleep
PubMed: 3659097
DOI: 10.1016/0091-3057(87)90202-4 -
Proceedings of the National Academy of... Jan 1981Binding sites for [3H]muscimol, an analogue of gamma-aminobutyric acid (GABA) were localized in the synaptic layers of chicken retina by light microscopic and electron...
Binding sites for [3H]muscimol, an analogue of gamma-aminobutyric acid (GABA) were localized in the synaptic layers of chicken retina by light microscopic and electron microscopic autoradiography. Light microscopic autoradiography of cryostat sections incubated in [3H]muscimol or [3H]GABA revealed identical binding patterns: a band over the inner plexiform layer (IPL) and a band over the outer plexiform layer (OPL). This binding pattern differed from the uptake pattern for [3H]GABA: labeling over horizontal, amacrine, and ganglion cell bodies as well as very intense labeling over lamina 5 in the proximal IPL. Statistical analysis of electron microscopic autoradiography data from the IPL indicated that only amacrine synapses bind [3H]muscimol (i.e., make GABAergic synapses). Processes of amacrine, bipolar, or ganglion cells can be postsynaptic to these amacrine synapses. The highest concentration of synapses binding [3H]muscimol occurred in laminae 2 and 4 of the IPL and not in lamina 5 as might be expected from the density of [3H]GABA uptake. In the OPL, [3H]muscimol binding occurred over specialized junctions proximal to photoreceptor terminals. In cone receptor terminals, [3H]muscimol binding was suspected near horizontal cell dendrite/receptor terminal membranes lateral to the synaptic ribbon, supporting the hypothesis that horizontal cells are involved in a GABAergic feedback loop with cone terminals. We conclude that the synaptic binding pattern provides a more accurate concept of GABAergic synaptic interaction than does the uptake pattern for [3H]GABA because the two patterns in the IPL are not related.
Topics: Animals; Autoradiography; Binding, Competitive; Chickens; Microscopy, Electron; Muscimol; Oxazoles; Receptors, Cell Surface; Receptors, Drug; Receptors, GABA-A; Retina; Synapses; gamma-Aminobutyric Acid
PubMed: 6264454
DOI: 10.1073/pnas.78.1.643 -
Journal of Neurosurgery Dec 2005The activity of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, is reduced in the hippocampus in patients with complex partial seizures from...
OBJECT
The activity of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, is reduced in the hippocampus in patients with complex partial seizures from mesial temporal sclerosis. To provide preliminary safety and distribution data on using convection-enhanced delivery of agents to treat complex partial seizures and to test the efficacy and safety of regional selective neuronal suppression, the authors infused muscimol, a GABA-A receptor agonist, directly into the hippocampus of nonhuman primates using an integrated catheter electrode.
METHODS
Ten rhesus monkeys were divided into three groups: 1) use of catheter electrode alone (four monkeys); 2) infusion of escalating concentrations of muscimol followed by vehicle (three monkeys); and 3) infusion of vehicle and subsequent muscimol mixed with muscimol tracer (three monkeys). Infusions were begun 5 days after catheter electrode placement and continued for 5.6 days before switching to the other agent. Head magnetic resonance (MR) images and electroencephalography recordings were obtained before and during the infusions. Brain histological studies and quantitative autoradiography were performed. Neurological function was normal in controls and when muscimol concentrations were 0.125 mM or less, whereas higher concentrations (0.5 and 1 mM) produced reversible apathy and somnolence. Fluid distribution was demonstrated on MR images and muscimol distribution was demonstrated on autoradiographs throughout the hippocampus and adjacent white matter.
CONCLUSIONS
Targeted modulation of neuronal activity is a reasonable research strategy for the investigation and treatment of medically intractable epilepsy.
Topics: Animals; Autoradiography; Brain; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Delivery Systems; Electroencephalography; Female; GABA Agonists; Hippocampus; Macaca mulatta; Magnetic Resonance Imaging; Male; Muscimol; Osmolar Concentration; Tissue Distribution
PubMed: 16381190
DOI: 10.3171/jns.2005.103.6.1035 -
Alcohol (Fayetteville, N.Y.) Jan 2001The pedunculopontine tegmental nucleus (PPN) has been implicated in a variety of behavioral functions, including stimulus selection. Given the PPN interactions with the...
The pedunculopontine tegmental nucleus (PPN) has been implicated in a variety of behavioral functions, including stimulus selection. Given the PPN interactions with the mesolimbic system, it was considered important to determine its involvement in ethanol self-administration. Long-Evans male rats were trained to self-administer 10% ethanol by using a sucrose-substitution procedure. After implantation of cannula guides, microinjections of 30, 100, and 300 ng of muscimol into the PPN before the self-administration session were performed. Ethanol self-administration was decreased at the 300-ng dose, in a manner similar to the actions of dopamine agonists microinjected in the nucleus accumbens. It is hypothesized that loss of PPN cholinergic input to the mesolimbic system affects the integrative activity of the nucleus accumbens and underlies the observed change in ethanol self-administration behavior.
Topics: Alcohol Drinking; Animals; Conditioning, Operant; Dose-Response Relationship, Drug; GABA Agonists; Male; Mesencephalon; Muscimol; Rats; Rats, Long-Evans; Reaction Time; Self Administration; Ventral Tegmental Area
PubMed: 11282451
DOI: 10.1016/s0741-8329(00)00122-1 -
Neuroreport Jul 1994In order to assess the functional role of the parietal hand movement region, the anterior part of the lateral bank of the intraparietal sulcus (IPS), area AIP, in the...
In order to assess the functional role of the parietal hand movement region, the anterior part of the lateral bank of the intraparietal sulcus (IPS), area AIP, in the visual guidance of hand grasping, we reversibly inactivated several parts of this area with microinjections of Muscimol in a monkey trained to grasp objects of different shapes, sizes and orientations. During the local inactivation, some of the skilled patterns of finger movements were disrupted in the contralateral hand, due to the lack of preshaping to adjust the finger posture to the object; however, no major deficits in visual reaching were observed. The results suggest that area AIP plays a crucial role in the visual guidance of goal-directed hand movements.
Topics: Animals; Brain Mapping; Hand; Macaca; Male; Microinjections; Muscimol; Parietal Lobe; Psychomotor Performance; Time Factors
PubMed: 7948854
DOI: 10.1097/00001756-199407000-00029 -
Journal of Neurophysiology Jul 1998To evaluate smooth-pursuit (SP) function in the primate frontal eye field (FEF), microinjections of muscimol, a gamma-aminobutyric acid (GABA) agonist, were used to...
To evaluate smooth-pursuit (SP) function in the primate frontal eye field (FEF), microinjections of muscimol, a gamma-aminobutyric acid (GABA) agonist, were used to reversibly deactivate physiologically characterized sites in FEF. SP was severely impaired by deactivation at sites in the FEF's smooth eye movement region (FEFsem) located in the fundus and posterior bank of the macaque monkey's arcuate sulcus. These SP deficits were apparent immediately after the muscimol injection and persisted for several hours but recovered by the next day. SP was most drastically and consistently impaired for directions similar to the injected site's elicited smooth eye movement direction or to the optimal SP direction for its neuronal responses. Targets moving in these directions, usually ipsilateral to the injected hemisphere, were tracked primarily with saccades after the muscimol injection, the peak SP velocity being only 10-30% of preinjection velocity. SP in other directions, including contralateral, was less strongly affected. Initial SP acceleration in response to target motion onset was also significantly diminished, generally by approximately the same proportion as peak SP velocity. In contrast, saccades were largely unaffected by muscimol injections in FEFsem; nor was there an immediate effect on SP when control sites in the saccadic region of FEF (FEFsac) were deactivated, although a SP deficit often appeared 30-60 min after FEFsac injections, possibly reflecting diffusion of muscimol into neighboring FEFsem. These reversible SP deficits produced by muscimol inactivation within FEFsem are similar to permanent deficits caused by large aspiration lesions of FEF and indicate that inclusion of FEFsem is the critical factor determining whether FEF lesions impair SP. The severity of the reversible deficits found here indicates how extremely critical FEFsem is for normal highgain SP.
Topics: Animals; Arcuate Nucleus of Hypothalamus; Female; Functional Laterality; GABA Agonists; Macaca mulatta; Microinjections; Muscimol; Saccades; Time Factors; Visual Fields
PubMed: 9658064
DOI: 10.1152/jn.1998.80.1.458