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Jorge Aceves - One of the best experts on this subject based on the ideXlab platform.
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Circling Behavior elicited by cholinergic transmission in the substantia nigra pars compacta involvement of nicotinic and muscarinic receptors
Neuroscience, 1996Co-Authors: Jose L Gongoraalfaro, Salvador Hernandezlopez, Daniel Martinezfong, Gonzalo Flores, Jorge AcevesAbstract:The influence of cholinergic transmission within the substantia nigra pars compacta on Circling Behavior was assessed in male rats. Microinjection of physostigmine (6-37 nmol) into the caudal part of the substantia nigra pars compacta elicited a dose-dependent contralateral Circling. The Circling was inhibited 93 +/- 3% by the dopamine antagonist haloperidol (53 nmol) injected into the neostriatum 90 min before the injection of physostigmine (37 nmol) into the ipsilateral substantia nigra pars compacta. The effect of haloperidol was reversible, since the Circling Behavior was fully restored when physostigmine was applied to the same animals 24 h later. The Circling was completely blocked when physostigmine (37 nmol) was applied simultaneously with the muscarinic M1 antagonist pirenzepine (2 nmol). The M2 antagonist AF-DX 116 (2 nmol) only partially blocked the Circling induced by a lower dose of physostigmine (12 nmol). The nicotinic antagonist mecamylamine (5 nmol) also inhibited the Circling, but only during the 5 min following co-injection of the drugs. These results indicate that endogenous acetylcholine stimulates muscarinic and nicotinic receptors of nigrostriatal dopaminergic neurons which, in turn, increase their firing rate and cause the Circling Behavior. We conclude that the pedunculopontine cholinergic neurons, which innervate the substantia nigra pars compacta, modulate the motor Behavior by increasing the activity of dopaminergic nigrostriatal pathway.
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cholinergic stimulation of rostral and caudal substantia nigra pars compacta produces opposite effects on Circling Behavior and striatal dopamine release measured by brain microdialysis
Neuroscience, 1994Co-Authors: Salvador Hernandezlopez, Daniel Martinezfong, J L Gongoraalfaro, M G Rosales, Jorge AcevesAbstract:Turning in circles is among the Behaviors elicited by unilateral cholinergic stimulation of the substantia nigra. Recent studies have shown that microinjection of cholinergic agonists into the substantia nigra pars compacta increases dopamine release and turnover in the striatum of anesthetized rats [Hernandez-Lopez et al. (1992) Brain. Res. 598, 114-120; Blaha and Winn (1993) J. Neurosci, 13, 1035-1044]. In this study, the relationship between Circling Behavior and striatal dopamine release following cholinergic stimulation of the substantia nigra pars compacta neurons was assessed by brain microdialysis in awake rats. The results indicate that cholinergic stimulation of the substantia nigra pars compacta with the mixed nicotinic-muscarinic cholinergic agonist carbachol modulates striatal dopamine release, and this effect is accompanied by Circling Behavior and stereotypies. Microinjection of carbachol (109 nmol) in the caudal portions of the substantia nigra pars compacta induced contralateral Circling associated with an increase of dopamine release in neostriatum. On the contrary, ipsilateral Circling and reduction of striatal dopamine release was elicited when the same dose of the drug was applied in the rostral portions of the substantia nigra pars compacta. The above findings are in accordance with recent electrophysiological studies suggesting the existence of sub-populations of nigrostriatal dopaminergic neurons, and indicate that the substantia nigra pars compacta is functionally compartmentalized. We conclude that the cholinergic input to the substantia nigra pars compacta could modulate the motor Behavior through regulating the firing rate of nigrostriatal dopaminergic neurons and dopamine release in the neostriatum.
Melvin D Yahr - One of the best experts on this subject based on the ideXlab platform.
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comparative effects of repeated administration of dopamine agonists on Circling Behavior in rats
Journal of Neural Transmission, 2000Co-Authors: A Prikhojan, T Brannan, Melvin D YahrAbstract:A paucity of studies are available concerning the comparative therapeutic effectiveness of presently available dopamine agonist agents in the control of Parkinson symptoms. To provide a basis for resolving this issue, we measured the Circling response in unilaterally nigrotomized (6-OHDA) rats following the administration of ropinirole, pramipexole, pergolide, bromocriptine, and cabergoline. Cabergoline, and to a lesser extent pergolide, produced the most vigorous and longest lasting Circling response. This response was sustained with administration of these agents over a nine day period. Bromocriptine, pramipexole and ropinirole were all less effective. These results suggest that dopamine agonists whose effect is primarily on D1 and D2 receptors are more effective than those whose actions do not include D1 activation.
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effects of repeated administration of l dopa and apomorphine on Circling Behavior and striatal dopamine formation
Brain Research, 1998Co-Authors: T Brannan, A Prikhojan, Melvin D YahrAbstract:Abstract We tested the Circling response to l -DOPA and apomorphine administration in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Rats demonstrated a progressively diminished Circling response when l -DOPA–carbidopa was repeatedly administered at 120 min intervals. This decreasing response was not present when apomorphine was administered under the same conditions. We also perfused l -DOPA directly into the striatum in vivo of rats with an ipsilateral 6-OHDA nigrotomy at 60 min intervals and monitored striatal dopamine levels with the technique of brain microdialysis. Dopamine formation increased from the first to the fifth trial. This may be secondary to the decrease in uptake sites which accompanies the loss of striatal dopamine nerve terminals. We postulate that the continued presence of dopamine at striatal receptor sites conditions a short-term loss of dopamine receptor sensitivity and a consequent decreased Circling response. The observation that desensitization (as measured by decreasing Circling) was not present following repeated apomorphine administration may be attributable to its shorter duration of action. We also perfused l -DOPA into the striatum of normal rats and noted a progressive decrease in striatal dopamine levels from the first to the fifth trial. Since this occurred following direct administration of l -DOPA into the striatum, the decrease could not be accounted for by peripheral pharmacodynamics or bioavailability of l -DOPA in the striatum. Since this decrease in dopamine formation was seen only in the normal striatum, its relevance to the diminished Behavioral response is unclear.
Salvador Hernandezlopez - One of the best experts on this subject based on the ideXlab platform.
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Circling Behavior elicited by cholinergic transmission in the substantia nigra pars compacta involvement of nicotinic and muscarinic receptors
Neuroscience, 1996Co-Authors: Jose L Gongoraalfaro, Salvador Hernandezlopez, Daniel Martinezfong, Gonzalo Flores, Jorge AcevesAbstract:The influence of cholinergic transmission within the substantia nigra pars compacta on Circling Behavior was assessed in male rats. Microinjection of physostigmine (6-37 nmol) into the caudal part of the substantia nigra pars compacta elicited a dose-dependent contralateral Circling. The Circling was inhibited 93 +/- 3% by the dopamine antagonist haloperidol (53 nmol) injected into the neostriatum 90 min before the injection of physostigmine (37 nmol) into the ipsilateral substantia nigra pars compacta. The effect of haloperidol was reversible, since the Circling Behavior was fully restored when physostigmine was applied to the same animals 24 h later. The Circling was completely blocked when physostigmine (37 nmol) was applied simultaneously with the muscarinic M1 antagonist pirenzepine (2 nmol). The M2 antagonist AF-DX 116 (2 nmol) only partially blocked the Circling induced by a lower dose of physostigmine (12 nmol). The nicotinic antagonist mecamylamine (5 nmol) also inhibited the Circling, but only during the 5 min following co-injection of the drugs. These results indicate that endogenous acetylcholine stimulates muscarinic and nicotinic receptors of nigrostriatal dopaminergic neurons which, in turn, increase their firing rate and cause the Circling Behavior. We conclude that the pedunculopontine cholinergic neurons, which innervate the substantia nigra pars compacta, modulate the motor Behavior by increasing the activity of dopaminergic nigrostriatal pathway.
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cholinergic stimulation of rostral and caudal substantia nigra pars compacta produces opposite effects on Circling Behavior and striatal dopamine release measured by brain microdialysis
Neuroscience, 1994Co-Authors: Salvador Hernandezlopez, Daniel Martinezfong, J L Gongoraalfaro, M G Rosales, Jorge AcevesAbstract:Turning in circles is among the Behaviors elicited by unilateral cholinergic stimulation of the substantia nigra. Recent studies have shown that microinjection of cholinergic agonists into the substantia nigra pars compacta increases dopamine release and turnover in the striatum of anesthetized rats [Hernandez-Lopez et al. (1992) Brain. Res. 598, 114-120; Blaha and Winn (1993) J. Neurosci, 13, 1035-1044]. In this study, the relationship between Circling Behavior and striatal dopamine release following cholinergic stimulation of the substantia nigra pars compacta neurons was assessed by brain microdialysis in awake rats. The results indicate that cholinergic stimulation of the substantia nigra pars compacta with the mixed nicotinic-muscarinic cholinergic agonist carbachol modulates striatal dopamine release, and this effect is accompanied by Circling Behavior and stereotypies. Microinjection of carbachol (109 nmol) in the caudal portions of the substantia nigra pars compacta induced contralateral Circling associated with an increase of dopamine release in neostriatum. On the contrary, ipsilateral Circling and reduction of striatal dopamine release was elicited when the same dose of the drug was applied in the rostral portions of the substantia nigra pars compacta. The above findings are in accordance with recent electrophysiological studies suggesting the existence of sub-populations of nigrostriatal dopaminergic neurons, and indicate that the substantia nigra pars compacta is functionally compartmentalized. We conclude that the cholinergic input to the substantia nigra pars compacta could modulate the motor Behavior through regulating the firing rate of nigrostriatal dopaminergic neurons and dopamine release in the neostriatum.
Jose L Gongoraalfaro - One of the best experts on this subject based on the ideXlab platform.
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Circling Behavior induced by microinjection of serotonin reuptake inhibitors in the substantia nigra
Pharmacology Biochemistry and Behavior, 2002Co-Authors: Jose L Batagarcia, Francisco J Heredialopez, Fernando J Alvarezcervera, Gloria Arankowskysandoval, Jose L GongoraalfaroAbstract:Abstract The nigrostriatal dopaminergic neurons of the substantia nigra pars compacta (SNc) and the nondopaminergic neurons of the substantia nigra pars reticulata (SNr) receive a dense synaptic input from the serotonergic neurons of the raphe nuclei. To assess whether serotonin [5-hydroxytryptamine (5-HT)] spontaneously released at the substantia nigra could modulate motor activity, the 5-HT reuptake inhibitors (SRIs), duloxetine (6–12 nmol) and clomipramine (12 nmol), were unilaterally microinjected either into the SNc or the SNr of freely moving rats, and the Circling Behavior was counted with an automated rotometer. In the SNc, the main effect of the SRIs was a contraversive Circling Behavior that was not observed when applied at distances ≥0.2 mm above the SNc. The Circling induced by clomipramine was blocked by microinjection of haloperidol (53 nmol) into the ipsilateral neostriatum, suggesting that the Circling elicited by microinjection of the SRIs into the SNc depends on an intact striatal dopaminergic transmission. Microinjection of 5-HT (21 nmol) only produced a significant contraversive Circling response when it was coinjected with the SRIs. Pretreatment with methysergide (1 mg/kg ip), a nonselective 5-HT 2 antagonist, did not block the Circling elicited by microinjection of clomipramine into the SNc, either alone or in combination with 5-HT. However, microinjection of the 5-HT 2 antagonist mianserin (2 nmol) into the SNc partially inhibited the Circling induced by duloxetine (6 nmol), alone or coinjected with 5-HT. Since current theories of Circling Behavior hypothesize that the animal turns away from the cerebral hemisphere where dopamine neurotransmission predominates, these results suggest that the contraversive Circling induced by the unilateral microinjection of SRIs into the SNc could be mediated by a 5-HT-induced increase of firing frequency of nigrostriatal dopaminergic neurons. When applied into the SNr, clomipramine and duloxetine also elicited a contraversive Circling Behavior and enhanced the Circling induced by 5-HT. Systemic methysergide (1 mg/kg ip), but not intranigral mianserin (2 nmol), blocked the Circling elicited by microinjection of clomipramine into the SNr, either alone or in combination with 5-HT. These results suggest that 5-HT 2 -like receptors are involved in the contraversive Circling induced by enhancement of serotonergic transmission in the SNr.
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Circling Behavior elicited by cholinergic transmission in the substantia nigra pars compacta involvement of nicotinic and muscarinic receptors
Neuroscience, 1996Co-Authors: Jose L Gongoraalfaro, Salvador Hernandezlopez, Daniel Martinezfong, Gonzalo Flores, Jorge AcevesAbstract:The influence of cholinergic transmission within the substantia nigra pars compacta on Circling Behavior was assessed in male rats. Microinjection of physostigmine (6-37 nmol) into the caudal part of the substantia nigra pars compacta elicited a dose-dependent contralateral Circling. The Circling was inhibited 93 +/- 3% by the dopamine antagonist haloperidol (53 nmol) injected into the neostriatum 90 min before the injection of physostigmine (37 nmol) into the ipsilateral substantia nigra pars compacta. The effect of haloperidol was reversible, since the Circling Behavior was fully restored when physostigmine was applied to the same animals 24 h later. The Circling was completely blocked when physostigmine (37 nmol) was applied simultaneously with the muscarinic M1 antagonist pirenzepine (2 nmol). The M2 antagonist AF-DX 116 (2 nmol) only partially blocked the Circling induced by a lower dose of physostigmine (12 nmol). The nicotinic antagonist mecamylamine (5 nmol) also inhibited the Circling, but only during the 5 min following co-injection of the drugs. These results indicate that endogenous acetylcholine stimulates muscarinic and nicotinic receptors of nigrostriatal dopaminergic neurons which, in turn, increase their firing rate and cause the Circling Behavior. We conclude that the pedunculopontine cholinergic neurons, which innervate the substantia nigra pars compacta, modulate the motor Behavior by increasing the activity of dopaminergic nigrostriatal pathway.
Wolfgang Löscher - One of the best experts on this subject based on the ideXlab platform.
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Abnormal Circling Behavior in rat mutants and its relevance to model specific brain dysfunctions.
Neuroscience and biobehavioral reviews, 2009Co-Authors: Wolfgang LöscherAbstract:Circling or rotational Behavior is the most studied indicator of cerebral asymmetry in the rat. In humans, disturbances in cerebral asymmetry are involved in the etiology of several psychiatric disorders, including schizophrenia, Tourette syndrome and attention-deficit hyperactivity disorder. Abnormal rotational Behavior in rodents is indicative of either an imbalance of forebrain dopamine systems, particularly an imbalance of nigrostriatal function, or an inner ear disease affecting the vestibular (balance) system. Abnormally enhanced Circling Behavior has been described in several mutant rat and mouse strains both with and without defects of the vestibular system. However, the relationship between vestibular defects and lateralized Circling in rodents is only incompletely understood. In this review, we describe and discuss various spontaneous mutations associated with abnormal Circling Behavior in different rat strains and their potential relevance to model specific brain dysfunctions. The Circling rat mutants described in this review illustrate how genetic animal models may serve to study multifaceted brain functions and dysfunctions, including disorders of the basal ganglia and vestibular system.
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a novel black hooded mutant rat ci3 with spontaneous Circling Behavior but normal auditory and vestibular functions
Neuroscience, 2001Co-Authors: Alina Lessenich, Sven Lindemann, Anne Richter, H J Hedrich, Dirk Wedekind, Alexander Kaiser, Wolfgang LöscherAbstract:Abstract Abnormal Circling Behavior in rodents is usually attributed to vestibular dysfunction. In rats, all Circling mutants described previously have inner ear defects resulting in auditory and vestibular dysfunctions. Here, we describe a new mutant rat with abnormal spontaneous Circling Behavior but normal auditory and vestibular functions. The new Circling mutant rat was discovered in progeny of an apparently normal black-hooded (BH) rat inbred line [BH.7A(LEW)/Won] and was termed ci3, because we recently found two other mutant Circling rats (ci1 and ci2) in a Lewis (LEW) inbred rat strain. The ci3 mutant is characterized by Circling Behavior and locomotor hyperactivity, which occur in phases or bursts either spontaneously or in response to stress, e.g., when rats are transferred to a new environment. Video monitoring of undisturbed rats in their home cage during the light and dark periods showed that Circling Behavior is much more intense during the dark period, i.e., during the active phase of the animals. Most ci3 rats show a lateral preference in their rotational Behavior, i.e., they either rotate to the left or to the right. Brainstem auditory evoked potential testing and different tests of vestibular function did not disclose any auditory or marked vestibular defects in ci3 rats. Furthermore, no morphological abnormalities were seen during histological examination of the cochlear and vestibular nuclei in the brainstem. Neurochemical determination of dopamine and dopamine metabolite levels in striatum, nucleus accumbens and substantia nigra showed that ci3 rats have a significant asymmetry in striatal dopamine in that dopamine levels were significantly lower in the hemisphere contralateral to the preferred direction of turning. Consistent with this finding, immunohistological examination of dopaminergic neurons in substantia nigra and ventral tegmental area yielded a significant laterality in the medial part of substantia nigra pars compacta with a lower density of tyrosine hydroxylase-positive neurons in the contralateral hemisphere of mutant Circling rats, while no laterality was seen in unaffected rats of the background strain [BH.7A(LEW)/Won]. Thus, the novel mutant ci3 rat exhibits several features which clearly differ from previously described Circling rat or mouse mutants. The Behavioral phenotype occurs in the absence of auditory or obvious vestibular defects and is most likely a consequence of lateralized abnormalities found in the nigrostriatal circuit. Apart from the use of ci3 rats for studying the functional lateralization of brain functions, the ci3 mutant may serve as a new model for movement disorders with abnormal lateralization.
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Spontaneous paroxysmal Circling Behavior in the ci2 rat mutant: epilepsy with rotational seizures or hyperkinetic movement disorder?
Experimental neurology, 2001Co-Authors: Sven Lindemann, Alina Lessenich, Ulrich Ebert, Wolfgang LöscherAbstract:Circling, turning, rotating, spinning, wheeling, and cursive hyperkinesia are all synonymous terms used to describe the active movement of an animal in a circular direction. Circling Behavior can be evoked by unilateral electrical and chemical stimulation or lesions of various brain sites, but can also occur after systemic drug administration or spontaneously in normal animals or mutant rodents. In humans, stereotypic body rotation can occur as a distinctive entity of generalized and focal epilepsy, and may be due to involvement of the striatum. We have previously described a Lewis rat mutant (ci2) with a Behavioral phenotype characterized by lateralized Circling, hyperactivity, opisthotonus, and ataxia. In these rats, Circling occurs in phases or bursts either spontaneously or in response to stress. Neurochemical data indicate that the Circling Behavior of the ci2 mutants is related to an abnormal asymmetry in dopaminergic activity in the striatum. Because of the similarities to rotational epilepsy, we used video and electroencephalographic recordings to study whether the rotational Behavior of the ci2 mutant rat is a result of a partial or generalized epilepsy. Epileptic WAG/Rij rats were used for comparison. Video monitoring of ci2 rats in the absence of any stress or disturbance showed that Circling occurs in paroxysmal bursts during active wakefulness, but not during passive wakefulness or sleep. Circling was not preceded or followed by any convulsive motor seizures and was not associated with epileptiform abnormalities in the electroencephalogram, whereas WAG/Rij rats exhibited myoclonic seizures and epileptic spike-wave discharges during passive wakefulness and sleep. As a result of the association of Circling with active wakefulness, ci2 rats exhibited many more rotations during the dark (active) phase compared with the light (rest) period. Increase in active wakefulness during the light phase by transfer of the rats to a new environment induced or intensified Circling Behavior. Most ci2 rats showed a consistent lateral preference during Circling, but some rats changed their preference from one session to another. The data indicate that spontaneous paroxysmal Circling Behavior in the ci2 rat is not a consequence of epilepsy but reflects a hyperkinetic movement disorder with abnormal lateralization of brain function.