Jaw Movements In Rats Research Articles

Expression of Concern: Neuroanatomical correlates of the inhibition of tremulous jaw movements in rats by a combination of memantine and Δ9 -tetrahydrocannabinol.

Expression of Concern: Neuroanatomical correlates of the inhibition of tremulous jaw movements in rats by a combination of memantine and Δ9 -tetrahydrocannabinol.

Neuroanatomical correlates of the inhibition of tremulous jaw movements in rats by a combination of memantine and Δ9 -tetrahydrocannabinol.

Memantine and marijuana smoking have been found to inhibit tremor in parkinsonian patients, although the observed effects were relatively weak. The tremorolytic effects of combinations of memantine and cannabinoids have not been studied. Here, we have evaluated the anti-tremor activity of memantine, Δ9 -tetrahydrocannabinol (THC) given alone and of their combination. The involvement of some neuroanatomical structures in the effects of the combination was evaluated. Haloperidol-induced tremulous jaw movements (TJMs) in rats were used as a model of parkinsonian-like tremor. To evaluate the role of central receptor systems in the drug effects, receptor ligands were administered locally into certain brain areas. Memantine and THC alone were without effect, although co-administration of these drugs decreased the number of haloperidol-induced jaw movements. The anti-tremor activity of the combination was antagonized (a) by injections of l-glutamate into the dorsal striatum, entopeduncular nucleus, substantia nigra pars reticulata, globus pallidus, and supratrigeminal and trigeminal motor nuclei but not into the subthalamic and cuneiform nuclei; (b) by injections of CGS 21680 into the ventrolateral striatum; and (c) by injections of bicuculline into the rostral part of the parvicellular reticular nucleus. Memantine and THC supra-additively inhibit haloperidol-induced TJMs, suggesting that co-administration of these drugs might be a new approach to the treatment of tremor. Our results identified brain areas influencing parkinsonian-like tremor in rats and can help advance the development of novel treatments for repetitive involuntary movements.

Effects of cabergoline and rotigotine on tacrine-induced tremulous jaw movements in rats

ObjectivesWe examined the effects of two dopamine agonists, cabergoline and rotigotine, on tacrine-induced tremor and c-Fos expression in rats. MethodsRats received intraperitoneal injection of cabergoline (0.5, 1.0, or 5.0mg/kg), rotigotine (1.0, 2.5, or 10.0mg/kg), or vehicle 30min before intraperitoneal injection of tacrine (5.0mg/kg). The number of tremulous jaw movements (TJMs) after tacrine administration was counted for 5min. Animals were sacrificed 2h later under deep anesthesia, and the brain sections were immunostained in order to evaluate the c-Fos expression. ResultsInduction of TJMs by tacrine was dose-dependently reduced by pretreatment with cabergoline and rotigotine. The number of c-Fos-positive cells was significantly enhanced in the medial striatum, nucleus accumbens core, and nucleus accumbens shell after tacrine administration, and the enhanced expression of c-Fos in these three regions was significantly attenuated by cabergoline, while rotigotine suppressed c-Fos expression in two regions except the nucleus accumbens core. ConclusionsThese results suggest that tacrine-induced TJMs would be relieved by either cabergoline or rotigotine and that anticholinesterase-induced TJMs and the ameliorating effects of dopamine agonists would relate to neuronal activation in the striatum and nucleus accumbens.

Apomorphine‐induced modulation of neural activities in the ventrolateral striatum of rats

The dopaminergic system in the ventrolateral portion of the striatum (Svl), part of the basal ganglia, regulates orofacial movements; bilateral co-stimulation of both dopamine D1 -like and D2 -like receptors elicits repetitive jaw movements in rats. However, how the activities of Svl neurons are modulated by the activation of dopaminergic receptors remains unknown. We systematically injected apomorphine, a non-selective dopamine receptor agonist that induced jaw movements under urethane anesthesia, and performed multi-channel unit recording from Svl neurons. The Svl neurons were classified into two subgroups: (1) the phasically active (PA) neurons represented by mainly the medium spiny neurons and the GABAergic interneurons in part, and (2) the tonically active (TA) neurons composed of mainly the cholinergic interneurons. Apomorphine modulated PA neuron firing frequency with wide variability; 33.3% of the PA neurons were facilitated, while 38.3% were suppressed. In the majority of TA neurons, the firing frequency was reduced by apomorphine (71.1%). The cross-correlations between PA and PA, PA and TA, and TA and TA neurons were analyzed, and pairs of PA neurons and pairs of PA and TA neurons, showed negligible apomorphine-induced effect on the number of synchronized spikes. In contrast, pairs between TA neurons showed a consistent decrease in the number of synchronized spikes. The apomorphine-induced suppression of TA neuron activities with decreased synchronized outputs is likely to reduce the amount of locally released acetylcholine, which may contribute to the induction of apomorphine-induced jaw movements in rats.

Conditional neural knockout of the adenosine A2A receptor and pharmacological A2A antagonism reduce pilocarpine-induced tremulous jaw movements: Studies with a mouse model of parkinsonian tremor

Tremulous jaw movements are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rats, tremulous jaw movements can be induced by a number of conditions that parallel those seen in human parkinsonism, including dopamine depletion, dopamine antagonism, and cholinomimetic drugs. Moreover, tremulous jaw movements in rats can be attenuated using antiparkinsonian agents such as L-DOPA, dopamine agonists, muscarinic antagonists, and adenosine A2A antagonists. In the present studies, a mouse model of tremulous jaw movements was established to investigate the effects of adenosine A2A antagonism, and a conditional neuronal knockout of adenosine A2A receptors, on cholinomimetic-induced tremulous jaw movements. The muscarinic agonist pilocarpine significantly induced tremulous jaw movements in a dose-dependent manner (0.25–1.0mg/kg IP). These movements occurred largely in the 3–7.5Hz local frequency range. Administration of the adenosine A2A antagonist MSX-3 (2.5–10.0mg/kg IP) significantly attenuated pilocarpine-induced tremulous jaw movements. Furthermore, adenosine A2A receptor knockout mice showed a significant reduction in pilocarpine-induced tremulous jaw movements compared to littermate controls. These results demonstrate the feasibility of using the tremulous jaw movement model in mice, and indicate that adenosine A2A receptor antagonism and deletion are capable of reducing cholinomimetic-induced tremulous jaw movements in mice. Future studies should investigate the effects of additional genetic manipulations using the mouse tremulous jaw movement model.

Neuronal activities of the vestibular nuclear complex during mechanically induced rhythmic jaw movements in rats

We studied the neuronal activities of the vestibular nuclear complex (VN) neurons during rhythmic jaw movements in rats anesthetized with urethane. Rhythmic jaw movements were induced by mechanical stimulation of the palate mucosa. The firing rate of approximately 25% of VN neurons increased significantly, and that of 10% of VN neurons decreased significantly, during these rhythmic jaw movements. There was no correlation between the change in the firing rate and the phase of the rhythmic jaw movements (jaw-opening and jaw-closing phases). The neurons that were affected were intermingled in the VN. These results suggest that the VN neurons are involved in controlling jaw movements.

Extracellular GABA in globus pallidus increases during the induction of oral tremor by haloperidol but not by muscarinic receptor stimulation

Tremulous jaw movements in rats can be induced by several conditions associated with parkinsonism and tremorogenesis, including dopamine depletion, dopamine antagonism, and cholinomimetic drugs. Previous research indicates that neostriatal mechanisms are involved in the generation of tremulous jaw movements, but the striatal output pathways involved in these movements remain uncertain. One important pathway for striatal output is the GABAergic striatopallidal system. The present studies were undertaken to determine if extracellular levels of GABA in globus pallidus are associated with the induction of tremulous jaw movements by either a dopamine D2 antagonist (haloperidol) or a cholinomimetic (the muscarinic agonist pilocarpine). The first experiment studied the effects of both acute and repeated (i.e. 8 days) administration of the D2 antagonist haloperidol. In the second experiment, the effect of acute administration of the muscarinic agonist pilocarpine on GABA levels in the globus pallidus was examined. In both experiments, behavioral observations of tremulous jaw movements were conducted in parallel with the collection of microdialysis samples. Acute and repeated haloperidol treatment induced tremulous jaw movements, and significantly elevated extracellular GABA in globus pallidus. Pooling across all treatment groups, there was a significant positive correlation between pallidal GABA levels and the number of tremulous jaw movements induced during the first three samples collected after injection. However, injection of 4.0mg/kg pilocarpine had no effect on pallidal GABA release, despite the robust induction of tremulous jaw movements. These results indicate that the tremulous jaw movements induced by dopamine D2 antagonism and those induced through muscarinic receptor stimulation may be generated via distinct mechanisms.

Effects of neck muscle activities during rhythmic jaw movements by stimulation of the medial vestibular nucleus in rats

This study first examines whether there is rhythmic activity of the neck muscles during cortically induced rhythmic jaw movements in rats anesthetized by urethane. Rhythmic jaw movements were induced by repetitive electrical stimulation of the orofacial motor cortex. An electromyogram in the splenius muscles (spEMG) showed rhythmic bursts during the jaw-opening phase, or during the transition from the jaw-opening phase to the jaw-closing phase. In the sternomastoid (stEMG), however, the electromyogram did not show any bursts during rhythmic jaw movements. A further study then examines whether stimulation of the medial vestibular nucleus (MVN) modulates the rhythmic activity of the neck muscles. Stimuli applied in the jaw-closing phase induced a transient burst in the stEMG, and the duration of activity in the spEMG was increased. Stimuli applied in the jaw-opening phase induced a transient burst in the stEMG and an inhibitory period in the spEMG. These results imply that the MVN is involved in the modulation of neck muscle activities during rhythmic jaw movements induced by stimulating the orofacial motor cortex.

Oral tremor induced by galantamine in rats: A model of the parkinsonian side effects of cholinomimetics used to treat Alzheimer's disease

Anticholinesterases are the most common treatment for Alzheimer's disease, and, in recent years, a new group of cholinesterase inhibitors (i.e. rivastigmine, galantamine, and donepezil) has become available. Although these drugs improve cognitive symptoms, they also can induce or exacerbate parkinsonian symptoms, including tremor. The present studies were conducted to determine if galantamine induces tremulous jaw movements, a rodent model of parkinsonian tremor, and to investigate whether these oral motor impairments can be reversed by co-administration of adenosine A2A antagonists. The first experiment demonstrated that systemic injections of galantamine (0.75–6.0mg/kg I.P.) induced a dose-related increase in tremulous jaw movements in rats. In a second study, co-administration of the muscarinic antagonist scopolamine (0.0156–0.25mg/kg I.P.) produced a dose dependent suppression of tremulous jaw movements induced by a 3.0mg/kg dose of galantamine, indicating that galantamine induces these tremulous oral movements through actions on muscarinic acetylcholine receptors. In two additional studies, analyses of freeze-frame video and electromyographic activity recorded from the lateral temporalis muscle indicated that the local frequency of these galantamine-induced jaw movements occurs in the 3–7Hz frequency range that is characteristic of parkinsonian tremor. In the final experiment, the adenosine A2A antagonist MSX-3 significantly attenuated the tremulous jaw movements induced by the 3.0mg/kg dose of galantamine, which is consistent with the hypothesis that co-administration of adenosine A2A antagonists may be beneficial in reducing parkinsonian motor impairments induced by anticholinesterase treatment.

Efficacy of zonisamide in a case of Parkinson’s disease with intractable resting and re-emergent tremor

Sirs, Zonisamide (ZNS) was originally used as an anti-epileptic agent. ZNS has recently been shown to exert beneficial effects in patients with Parkinson s disease (PD) [1–6] and anti-tremor effects in patients with essential tremor and in tacrine-induced tremulous jaw movements in rats [7–11]. We report herein that intractable resting and re-emergent tremor [12] (resting tremor that re-emerges after a variable delay while maintaining posture) in patients with PD improved dramatically by ZNS. This case was a 73-year-old woman with PD who developed resting tremor and mild postural tremor on the right hand at the age of 68 years. The patient first took pramipexole, but the dosage could not be increased because of adverse effects of sleepiness, and so was kept at 1.5 mg/day. After 2 years, resting tremors expanded to all extremities, and postural tremor appeared on both upper hands. Levodopa/carbidopa at 500 mg/day, cabergoline and amantadine showed no efficacy against tremors. Trihexyphenidyl at 2 mg/day decreased tremors (Video S1), but induced somnolence. Alotinolol could not be used, as the patient was asthmatic. After 4 years, activities of daily living deteriorated because of severe resting and re-emergent tremors on both upper hands, as well as jaw and tongue tremors (Video S1). She was unable to change clothes or eat meals by herself even using daily doses of pramipexole at 1.5 mg, levodopa/carbidopa at 500 mg and trihexyphenidyl at 4 mg. ZNS was added at 50 mg/day, and tremors diminished slightly. Resting and re-emergent tremors improved markedly with ZNS at 100 mg/day (Video S2). Although mild sleepiness was observed, no severe additional adverse effects were noted during treatment with ZNS. Her

Modulation of cortically induced rhythmic jaw movements in rats by stimulation of the vestibular nuclear complex

We study whether stimulation of the vestibular nuclear (VN) complex can modulate rhythmic jaw movements in rats anesthetized by urethane. Rhythmic jaw movements were induced by repetitive electrical stimulation of the orofacial motor cortex. Stimulation of the medial vestibular nucleus (MVN) during the jaw-closing phase increased the amplitude of the jaw-closing movement. (This is not a movement that continues to closure.) Stimulation of the MVN during the jaw-opening phase disturbed the rhythm of jaw movements and induced a small jaw-closing movement. Stimulation of the superior VN (SVN) and the lateral VN (LVN) during the jaw-closing phase did not affect the amplitude of the jaw-closing movement. Stimulation of the SVN and the LVN during the jaw-opening phase increased the amplitude of the jaw-opening movement, however. Stimulation of the inferior VN during the jaw-closing and the jaw-opening phase, respectively decreased the amplitude of the jaw-closing and the jaw-opening movements. Stimulation applied outside the VN did not modulate the amplitude of the jaw movements. These results imply that the VN is involved in the modulation of rhythmic jaw movements induced by stimulation of the orofacial motor cortex.

Oral tremor induced by the muscarinic agonist pilocarpine is suppressed by the adenosine A 2A antagonists MSX-3 and SCH58261, but not the adenosine A 1 antagonist DPCPX

Tremulous jaw movements in rats, which can be induced by dopamine (DA) antagonists, DA depletion, and cholinomimetics, have served as a useful model for studies of tremor. Although adenosine A 2A antagonists can reduce the tremulous jaw movements induced by DA antagonists and DA depletion, there are conflicting reports about the interaction between adenosine antagonists and cholinomimetic drugs. The present studies investigated the ability of adenosine antagonists to reverse the tremorogenic effect of the muscarinic agonist pilocarpine. While the adenosine A 2A antagonist MSX-3 was incapable of reversing the tremulous jaw movements induced by the 4.0 mg/kg dose of pilocarpine, both MSX-3 and the adenosine A 2A antagonist SCH58261 reversed the tremulous jaw movements elicited by 0.5 mg/kg pilocarpine. Systemic administration of the adenosine A 1 antagonist DPCPX failed to reverse the tremulous jaw movements induced by either an acute 0.5 mg/kg dose of the cholinomimetic pilocarpine or the DA D2 antagonist pimozide, indicating that the tremorolytic effects of adenosine antagonists may be receptor subtype specific. Behaviorally active doses of MSX-3 and SCH 58261 showed substantial in vivo occupancy of A 2A receptors, but DPCPX did not. The results of these studies support the use of adenosine A 2A antagonists for the treatment of tremor.

Effects of zonisamide on c-Fos expression under conditions of tacrine-induced tremulous jaw movements in rats: A potential mechanism underlying its anti-parkinsonian tremor effect

Objectives To examine the mechanisms underlying the anti-tremor effect of zonisamide in rats under conditions of tacrine-induced tremulous jaw movements (TJMs). Methods Male adult rats received systemic administration of either zonisamide (5 or 50 mg/kg) or vehicle at 20 min prior to the administration of tacrine hydrochloride (5 mg/kg). Animals were sacrificed 2 h later, and the brains collected and immunostained for quantitative assessment of c-Fos expression. Results There was no effect of zonisamide on tacrine-induced c-Fos expression in the ventrolateral striatum, a primary site of the pharmacological action of tacrine. Zonisamide suppressed the tacrine-induced c-Fos expression in the cortex, the dorsal striatum, and the nucleus accumbens, which are involved in the architecture of the cortico-basal ganglia-thalamocortical circuits. Conclusion The anti-TJM effect of zonisamide may not relate to suppression of neural activity specifically in primary tremor-generating sites, but may be due to a more broad inhibitory effect on tremor-related structures such as the cortex or the striatum. This effect of zonisamide may be a contributing mechanism underlying its therapeutic efficacy on parkinsonian tremor.

A 5-HT 2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model

A potent 5-hydroxytryptamine (5-HT) 2A receptor inverse agonist and antagonist, ACP-103 [ N-(4-fluorophenylmethyl)- N-(1-methylpiperidin-4-yl)- N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2 R,3 R)-dihydroxybutanedioate (2:1, active:salt)], was evaluated for its ability to reduce the primary motor symptom of tremor using tacrine-induced tremulous jaw movements in rats, which is an animal model of parkinsonian tremor. Furthermore, ACP-103 was evaluated for its ability to reduce levodopa-induced dyskinesias in monkeys rendered parkinsonian with MPTP [1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine]. ACP-103 reduced tacrine-induced tremulous jaw movements in rats. In addition, ACP-103 administered in combination with levodopa caused a dose-related reduction in dyskinesias in monkeys. These data suggest that ACP-103 may have the potential to reduce tremor and levodopa-induced dyskinesias in Parkinson's disease.

Tremorolytic effects of adenosine A2A antagonists: implications for parkinsonism

Drug-induced tremulous jaw movements in rats have been used as a model of parkinsonian tremor. Because adenosine A2A antagonists have antiparkinsonian effects, the present experiments were conducted to study the ability of adenosine A2A antagonism to reverse the tremulous jaw movements produced by the antipsychotic drugs pimozide, haloperidol and reserpine. In one group of studies, rats received daily injections of the dopamine antagonist pimozide, and on day 8 they received injections of pimozide plus various doses of the A2A antagonists KW 6002 or MSX-3. KW 6002 and MSX-3 suppressed pimozide-induced tremulous jaw movements, reduced catalepsy, and increased locomotion. MSX-3 also suppressed the jaw movements induced by haloperidol and reserpine. In addition, local injections of MSX-3 into the ventrolateral neostriatum suppressed pimozide-induced tremulous jaw movements. Thus, adenosine A2A antagonism can reverse the tremulous movements induced by antipsychotic drugs, which is consistent with the hypothesis that antagonism of adenosine A2A receptors can result in antiparkinsonian effects. Adenosine A2A antagonists may be useful for their tremorolytic effects, and may help in treating both idiopathic and antipsychotic-induced parkinsonian symptoms.

5-HT1A and 5-HT1B receptors in the ventrolateral striatum differentially modulate apomorphine-induced jaw movements in rats

The ability of serotonin 5-HT(1A) and 5-HT(1B) receptors in the ventrolateral striatum to modulate dopamine receptor-mediated jaw movements was investigated in freely moving rats, using a magnet-sensing system combined with an intracerebral drug microinjection technique. Apomorphine (1 mg/kg i.v.) has been found to elicit repetitive jaw movements. Bilateral injections of the 5-HT(1A) receptor agonist 8-OH-DPAT (1 and 4 microg/0.2 microl in each side) into the ventrolateral striatum partially but significantly reduced apomorphine-induced repetitive jaw movements. The 5-HT(1A) receptor antagonist WAY-100635 (1 microg), which alone did not affect the effects of apomorphine, antagonized the inhibitory effects of 8-OH-DPAT (4 microg). Bilateral injections of the 5-HT(1B) receptor agonist CP93129 (1 and 10 microg) also reduced apomorphine-induced repetitive jaw movements in a dose-dependent manner. However, the 5-HT(1B) receptor antagonist GR55562 (1 and 10 microg) did not antagonize the inhibitory effects of CP93129 (10 microg). These results suggest that 5-HT(1A), but not 5-HT(1B), receptors in the ventrolateral striatum play a modulatory role in the production of dopamine receptor-mediated jaw movements.

Modulation of cortically induced rhythmical jaw movements by stimulation of the red nucleus in the rat

We study whether stimulation of the red nucleus (RN) can modulate rhythmical jaw movements in rats anesthetized by urethane. Rhythmical jaw movements were induced by repetitive electrical stimulation of the two cortical masticatory areas (area A: the orofacial motor cortex; area P: the insular cortex). Stimuli applied to the RN did influence rhythmical jaw movements induced by stimulation of the A-area. Stimuli applied in the jaw-closing phase increased the amplitude of the jaw-closing movement. Stimuli applied in the jaw-opening phase disturbed the rhythm of jaw movements and induced a small jaw-closing movement. Stimuli applied to the RN did not influence rhythmical jaw movements induced by stimulation of the P-area. These results indicate that the RN is involved in the modulation of rhythmical jaw movements induced by stimulation of the A-area.

The effect of chronic administration of sarizotan, 5-HT1A agonist/D3/D4 ligand, on haloperidol-induced repetitive jaw movements in rat model of tardive dyskinesia

Dyskinesia is the most troublesome side effect in long-term treatment of both Parkinson's disease (PD) and schizophrenia. The 5-HT1A agonist and D3/D4 ligand sarizotan [Bartoszyk, G.D., van Amsterdam, C., Greiner, H.E., Rautenberg, W., Russ, H., Seyfried, C.A., 2004. Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile. J. Neural Transm. 111, 113–126.] is in clinical development for the treatment of PD-associated dyskinesia. Because 5-HT 1A agonists are known to counteract antipsychotic-induced motor side effects, sarizotan was investigated for its effects in two rat models of tardive dyskinesia (TD). The acute administration of sarizotan (0.17–13.5 mg/kg i.p.) reduced episodes of SKF 38393-induced repetitive jaw movements (RJM) in rats with a maximal effect at 1.5 mg/kg. In a chronic study, sarizotan (0.04–9 mg/kg/day), administered in the drinking water for 7 weeks during withdrawal from chronic haloperidol treatment (1.5 mg/kg/day), dose-dependently reversed haloperidol-induced RJM, significant at the doses of 1.5 and 9 mg/kg. Agonism at 5-HT1A receptors may be mediating the inhibitory effect of sarizotan on RJM in rat models of tardive dyskinesia.

Quetiapine (Seroquel) shows a pattern of behavioral effects similar to the atypical antipsychotics clozapine and olanzapine: studies with tremulous jaw movements in rats

Previous studies demonstrated that clozapine and olanzapine suppressed tacrine-induced jaw movements at lower doses than those required for suppression of lever pressing. The present studies were undertaken to evaluate the novel atypical antipsychotic quetiapine using the jaw movement model. The effect of acute quetiapine on the suppression of tacrine-induced tremulous jaw movements was examined. To determine the relative potency of this effect compared with other behavioral effects of quetiapine, suppression of lever pressing also was studied. In other studies, rats received quetiapine for 14 consecutive days to study the effects of repeated injections of this drug. Acute quetiapine injections decreased tacrine-induced jaw movements and lever pressing. The ratio of the ED50 for suppression of jaw movements divided by the ED50 for suppression of lever pressing was used as an index of liability to produce motor side effects, and the present results demonstrate that quetiapine has a ratio similar to that previously shown for clozapine and olanzapine. In the repeated-administration studies, quetiapine failed to induce jaw movements. On day 14, quetiapine reduced tacrine-induced tremulous jaw movements, and in a parallel experiment quetiapine significantly suppressed lever pressing on days 1-14. Repeated injections of quetiapine reduced tacrine-induced jaw movements over a dose range lower than that required for suppression of lever pressing. On tests of jaw movement activity and lever pressing after both acute and repeated drug administration, quetiapine showed a profile somewhat similar to clozapine and olanzapine. A theoretical model is offered suggesting that atypical antipsychotics that act on 5-HT or muscarinic receptors have intrinsic antiparkinsonian actions that work in opposition to the motor effects produced by dopamine antagonism.

The GABA uptake inhibitor β-alanine reduces pilocarpine-induced tremor and increases extracellular GABA in substantia nigra pars reticulata as measured by microdialysis

Substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia that receives GABAergic projections from neostriatum and globus pallidus. Previous research has shown that local pharmacological manipulations of GABA in SNr can influence tremulous jaw movements in rats. Tremulous jaw movements are defined as rapid vertical deflections of the lower jaw that resemble chewing but are not directed at a particular stimulus, and evidence indicates that these movements share many characteristics with parkinsonian tremor in humans. In order to investigate the role of GABA in motor functions related to tremor, the present study tested the GABA uptake blocker β-alanine for its ability to reduce pilocarpine-induced tremulous jaw movements. In a parallel experiment, the effect of an active dose of β-alanine on dialysate levels of GABA in SNr was assessed using microdialysis methods. GABA levels in dialysis samples were measured using high performance liquid chromatography with electrochemical detection. β-Alanine (250–500 mg/kg) significantly reduced tremulous jaw movements induced by pilocarpine (4.0 mg/kg). Moreover, systemic administration of β-alanine at a dose that reduced tremulous jaw movements (500 mg/kg) resulted in a substantial increase in extracellular levels of GABA in SNr compared to the pre-injection baseline. Thus, the present results are consistent with the hypothesis that GABAergic tone in SNr plays a role in the regulation of tremulous jaw movements. This research may lead to a better understanding of how parkinsonian symptoms are modulated by SNr GABA mechanisms.