-
Life Sciences Sep 1983The substantia nigra plays a pivotal role in the relay of output from the striatum. One neural pathway from substantia nigra projects GABAergic fibers to the caudal...
The substantia nigra plays a pivotal role in the relay of output from the striatum. One neural pathway from substantia nigra projects GABAergic fibers to the caudal mesencephalic tegmentum, terminating in the vicinity of the pedunculopontine nucleus (PPN). To evaluate the functional importance of this projection in the mediation of stereotyped behaviors of striatal and nigral origin, we microinjected low doses of the GABA agonist, muscimol, bilaterally into the vicinity of the PPN. This muscimol treatment resulted in a total blockade of all stereotyped behaviors normally elicited by systemic apomorphine or by intranigral muscimol. Blockade was not observed in animals microinjected with muscimol into the dorsal reticular formation, 1 mm above the level of the PPN. Our results indicate that the nigrotegmental projection may play a crucial role in the expression of stereotyped and dyskinetic behaviors of basal ganglia origin.
Topics: Animals; Apomorphine; Corpus Striatum; Humans; Male; Muscimol; Neural Pathways; Oxazoles; Pons; Rats; Rats, Inbred Strains; Stereotyped Behavior; Substantia Nigra; Tegmentum Mesencephali; gamma-Aminobutyric Acid
PubMed: 6684199
DOI: 10.1016/0024-3205(83)90758-0 -
Talanta Jul 2014The CE-ESI-MS/MS method for the identification, separation and determination of mushroom toxins, namely ibotenic acid, muscimol and muscarine, was developed. It proved...
The CE-ESI-MS/MS method for the identification, separation and determination of mushroom toxins, namely ibotenic acid, muscimol and muscarine, was developed. It proved to be sensitive and thus useful for the real sample analysis with omitting the labor and time consuming pretreatment step. The CE-ESI-MS/MS method was applied on the spiked human urine. The analytical characteristics of the proposed method, such as limits of detection, linearity and repeatability of the peak area and the migration time, were evaluated. The RSD of the migration time and peak area were from 0.93% to 1.60% and from 2.96% to 3.42%, respectively. The obtained LOD values were at the nanomolar concentration level, therefore the developed method is sufficient for the determination and quantification of studied toxins in human urine after mushroom intoxication.
Topics: Agaricales; Electrophoresis, Capillary; Humans; Ibotenic Acid; Limit of Detection; Muscarine; Muscimol; Mushroom Poisoning; Osmosis; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Urinalysis
PubMed: 24840440
DOI: 10.1016/j.talanta.2014.03.019 -
Neurobiology of Learning and Memory Jul 2023We have previously shown that the rat prelimbic cortex (PL) is necessary for contexts to promote the performance of instrumental behaviors that have been learned in...
We have previously shown that the rat prelimbic cortex (PL) is necessary for contexts to promote the performance of instrumental behaviors that have been learned in them, whether the context is physical (operant chamber) or behavioral (recent performance of a behavior that has historically preceded the target in a behavior chain). In the present experiment, we investigated the role of the PL in satiety level as an interoceptive acquisition context. Rats were trained to lever-press for sweet/fat pellets while sated (22 hrs continuous food access) followed by the extinction of the response while hungry (22 hrs food deprived). Pharmacological inactivation of the PL (with baclofen/muscimol infusion) attenuated renewal of the response that occurred upon a return to the sated context. In contrast, animals that received a vehicle (saline) infusion showed renewal of the previously extinguished response. These results support the hypothesis that the PL monitors the relevant contextual elements (physical, behavioral, or satiety state) associated with reinforcement of a response and promotes the subsequent performance of that response in their presence.
Topics: Rats; Animals; Conditioning, Operant; Extinction, Psychological; Prefrontal Cortex; Reinforcement, Psychology; Muscimol
PubMed: 37119848
DOI: 10.1016/j.nlm.2023.107759 -
Experimental Brain Research 19911.) Eye movements were recorded in four Java monkeys (M. fascicularis) after unilateral microinjections (1 microliter, concentration 1 micrograms/microliter) of the GABA...
1.) Eye movements were recorded in four Java monkeys (M. fascicularis) after unilateral microinjections (1 microliter, concentration 1 micrograms/microliter) of the GABA antagonist, bicuculline, and the GABA agonist, muscimol, into oculomotor related regions of the vestibular nuclei. Eye movements were investigated in the dark and light during spontaneous eye movements, vestibular stimulation (sinusoidal: 0.2 Hz, +/- 40 deg/s, and velocity trapezoid: 40 deg/s2 acceleration, 120 deg/s constant velocity), and visual-vestibular conflict stimulation. 2.) Bicuculline and muscimol injections consistently led to specific eye movement changes, which were maximal 5-10 min after bicuculline injection (muscimol 10-30 min), and lasted 90-120 min (muscimol 2-4 h). Control injections with NaCl (0.9%) into the responsive area and with bicuculline 2-3 mm more lateral showed no effect. 3.) Bicuculline induced a spontaneous nystagmus of 40.9 deg/s (average, range 10.5-93 deg/s), beating in 60% of the cases to the contralateral and in 40% to the ipsilateral side. The analysis of the slope of the slow phase gave no evidence for an additional gaze holding deficit. The VOR gain in the dark showed a slight decrease (pre: 0.96; post: 0.86) on average. The time constant of decay for slow phase nystagmus velocity after vestibular ramp stimulation was reduced, reflecting a 'velocity storage' deficit. After bicuculline injections nystagmus suppression in the light and during visual-vestibular conflict stimulation was generally well preserved. 4.) After muscimol injections horizontal gaze holding was severely affected. Each saccade was followed by an exponentially decreasing postsaccadic drift with a time constant as short as 250 ms (average 414 ms). The eyes always drifted towards a null-position, which generally did not coincide with the midposition of the eye. The null-position could move up to 35 deg to the contralateral or ipsilateral side. The highly distorted eye movements after muscimol injections prevented VOR-measurements based on eye velocity. Instead vestibular stimulation led to a shift of the null-position with an amplitude corresponding to a gain (eye position/stimulus position) of 0.17 (average) at 0.2 Hz (+/- 40 deg/s). Vertical eye movements did not show a major gaze holding deficit. 5.) From the experiments it can be concluded that the inhibitory transmitter GABA plays an important role for eye movement generation within the vestibular nuclei. Bicuculline induces mainly a vestibular imbalance with little evidence for a neural integrator deficit. In contrast unilateral muscimol injections lead to a complete, reversible loss of function for the common horizontal neural integrator, which converts eye velocity into eye position signals. The accompanying shift of the null-position reflects an additional vestibular imbalance.
Topics: Animals; Bicuculline; Conflict, Psychological; Darkness; Electrodes, Implanted; Eye Movements; Light; Macaca fascicularis; Microelectrodes; Microinjections; Muscimol; Photic Stimulation; Reflex, Vestibulo-Ocular; Vestibular Nuclei
PubMed: 1756810
DOI: 10.1007/BF00228958 -
Neuroscience Letters Aug 1991The role of gamma-aminobutyric acid (GABA) in the sleep-waking cycle was evaluated by means of microinjections of muscimol and bicuculline into the rat pontine reticular...
The role of gamma-aminobutyric acid (GABA) in the sleep-waking cycle was evaluated by means of microinjections of muscimol and bicuculline into the rat pontine reticular formation (PRF). Muscimol (20 ng) produced a marked increase in wakefulness (70%), a decrease in slow-wave sleep (SWS) (35%) and a remarkable delay in the onset of both SWS and paradoxical sleep, without modifying the percentage of the latter. Bicuculline (4 ng) shortened SWS latency by about 70%. These results suggest that GABAergic transmission in the PRF is involved in the regulation of sleep-waking cycle in the rat.
Topics: Animals; Bicuculline; Male; Microinjections; Muscimol; Pons; Rats; Rats, Inbred Strains; Receptors, GABA-A; Reticular Formation; Sleep; Synaptic Transmission; Wakefulness
PubMed: 1656343
DOI: 10.1016/0304-3940(91)90728-c -
Japanese Journal of Pharmacology Jun 1979
Topics: Animals; Catalepsy; Humans; Injections, Intraventricular; Locomotion; Male; Muscimol; Oxazoles; Rats
PubMed: 575395
DOI: 10.1254/jjp.29.496 -
The Journal of Neuroscience : the... Sep 1990Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D-[1-14C] glucose technique in 70 anatomically discrete central nervous...
Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D-[1-14C] glucose technique in 70 anatomically discrete central nervous structures in conscious awake rats following unilateral intranigral application of the GABAergic agonist muscimol. Intranigral injection of 1.3 microliters 1 microM muscimol (0.15 ng) induced increases in glucose consumption locally in the substantia nigra reticulata (by 87%), distally in the contralateral reticulata, red nucleus, nucleus accumbens, and prefrontal cortex, and bilaterally in the pyriform cortex, as compared to values in control animals. Intranigral injection of 1.3 microliters 1 mM muscimol (150 ng) effected a local metabolic activation in the substantia nigra reticulata (by 111% compared to the control group) and in compacta (by 18%), as well as a distal activation in the contralateral reticulata (by 39%) and contralateral compacta (by 29%). Beyond the structures affected by the lower dose, the higher dose of muscimol elicited widespread bilateral increases in glucose metabolism in the rat brain. Among the principal nigral reticulata efferent projections, the deep superior colliculi displayed ipsilateral metabolic activation (by 30%), whereas the parafascicular, mediodorsal, and ventromedial thalamic projecting areas, as well as the pedunculopontine nucleus, displayed bilateral activations compared to the control animals. The ventromedial and ventrolateral thalamic nuclei contralateral to the injected substantia nigra reticulata were 20% activated compared to the ipsilateral homologous structures and 30% activated compared to the control rats. The areas that send afferent projections to the reticulata (globus pallidus, entopeduncular and subthalamic nuclei) were mainly activated contralateral to the injected reticulata compared to values for control animals. In general, following intranigral muscimol (1 mM) injection, glucose metabolism was activated to a larger extent on the side contralateral to the injection than on the ipsilateral side. It is suggested that the present findings are due to a presynaptic nigral effect of muscimol on the GABAergic autoreceptors of the striatonigral terminals and to a consequent disinhibition of the reticulata GABAergic output.
Topics: Animals; Autoradiography; Brain; Brain Stem; Cerebellum; Deoxy Sugars; Deoxyglucose; Diencephalon; Energy Metabolism; Kinetics; Male; Mesencephalon; Muscimol; Rats; Rats, Inbred Strains; Substantia Nigra; Telencephalon
PubMed: 2398365
DOI: 10.1523/JNEUROSCI.10-09-02861.1990 -
Neuroreport Oct 1996To investigate how GABAA inhibition in the motor cortex is involved in motor control in freely moving infant macaque monkeys, muscimol, a GABAA agonist, was injected...
To investigate how GABAA inhibition in the motor cortex is involved in motor control in freely moving infant macaque monkeys, muscimol, a GABAA agonist, was injected into the hand motor area and changes in movement parameters of visual reaching during apple pickup tests or a delayed response task were examined. After the injection (30 micrograms microliters-1) the monkeys tended to use the contralateral hand, and the ipsilateral hand showed a posture of dropped wrist and fingers, as if the radial nerve were paralysed. Movement time and/or reaction time of the ipsilateral hand was prolonged. Motorcortical GABAA inhibition is important for initiation of smooth flexion and/or extension movement of the hand and fingers.
Topics: Animals; Dominance, Cerebral; Forelimb; GABA Agonists; Hand; Injections; Macaca; Macaca mulatta; Male; Motor Cortex; Movement; Muscimol; Psychomotor Performance; Receptors, GABA-A
PubMed: 8951856
DOI: 10.1097/00001756-199610020-00020 -
Journal of Medicinal Chemistry Oct 1992Ten analogs of muscimol and thiomuscimol in which the amino function was delocalized in an amidinic system were prepared by N2 alkylation of 6-aryl-3-aminopyridazines...
Ten analogs of muscimol and thiomuscimol in which the amino function was delocalized in an amidinic system were prepared by N2 alkylation of 6-aryl-3-aminopyridazines with (chloromethyl)isoxazole or (chloromethyl)isothiazole derivatives. These muscimol and thiomuscimol derivatives show potent binding properties for GABA-A receptors (they displace [3H]GABA and [3H]gabazine) and provoke convulsions after iv injections. They fit well with the model pharmacophore proposed by our group for the GABA-A antagonists and show similar structure-activity profiles to that of the pyridazinyl-GABAs.
Topics: Animals; Binding, Competitive; Convulsants; Female; GABA-A Receptor Antagonists; In Vitro Techniques; Mice; Models, Molecular; Molecular Conformation; Muscimol; Pyridazines; Radioligand Assay; Rats; Receptors, GABA-A; Structure-Activity Relationship
PubMed: 1331456
DOI: 10.1021/jm00100a015 -
Archives Internationales de... Oct 1981Muscimol (MU) was tested on mice for anticonvulsive action against chemical convulsants. 3-Mercaptopropionic acid (3-MP) was more sensitive to inhibition by MU (1.5...
Muscimol (MU) was tested on mice for anticonvulsive action against chemical convulsants. 3-Mercaptopropionic acid (3-MP) was more sensitive to inhibition by MU (1.5 mg/kg) than was either pentylenetretrazol (PTZ) or bicuculline (BIC); picrotoxin (PIC) and kainic acid were not measurably antagonized; aminophylline was potentiated. The profile of action of MU closely resembles that of aminooxyacetic acid (AOAA), except that the latter strongly antagonizes kainic acid. MU distinguished more clearly than did AOAA between the action of 3-MP and that of either PTZ or BIC, inasmuch as the differences between the respective potency ratios were larger with MU than with AOAA. The results are consistent with the view that MU acts as a GABA agonist, that GABA antagonism is not a sufficient basis on which to explain the convulsive action of BIC or PIC, and that the antagonism of AOAA toward seizures induced by kainic acid may not be due to an action on the GABA system.
Topics: Animals; Anticonvulsants; Convulsants; Male; Mice; Mice, Inbred ICR; Muscimol; Oxazoles
PubMed: 7325765
DOI: No ID Found