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PubMed1986

Effects of apomorphine on morphine analgesia during the state of dopaminergic supersensitivity after chronic treatment with haloperidol.

Morphine induced-reduction in response to a repetitive electrical stimulation of the tail was measured in acute rats and rats chronically treated with haloperidol (1 mg/kg/d, for 7 d) following pretreatment with apomorphine. In acute experiments, a significant enhancement of the anti-struggling action of morphine was produced by haloperidol (1 mg/kg, i.p.). Low doses of apomorphine (30-480 micrograms/kg, i.p.) had no influence on the suppressing action of morphine on the struggling response induced by the tail stimulation. Following chronic treatment with haloperidol, the inhibitory action of morphine on the tail stimulation-induced struggling response was dose-dependently inhibited by very low doses of apomorphine (60-480 micrograms/kg, i.p.). A significant increase in 3,4-dihydroxyphenylacetic acid (DOPAC) levels was observed after administration of haloperidol or morphine in acute rats, whereas no change in DOPAC levels was found after administration of morphine or apomorphine in chronically haloperidol-treated rats. In these animals, basal striatal DOPAC levels were significantly decreased compared with those of vehicle-treated animals controls. The present results suggest that in rats treated chronically with haloperidol, the suppressive action of a low dose of apomorphine on morphine analgesia is due to an increased sensitivity of postsynaptic dopaminergic receptors to apomorphine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

[Apomorphine: an alternative in the control of motor fluctuations in Parkinson's disease].

Levodopa-induced motor fluctuations (MF) is a disabling complication of Parkinson's disease (PD) and is usually refractory to conventional treatment. Apomorphine, a dopamine agonist with affinity for both D1 and D2 receptors, has been emerged as an useful alternative in the management of MF of PD. The frequency of nausea and vomiting prevented its use in the past, but the simultaneous administration of domperidone has proved to be able to control these side effects. Although apomorphine has been successfully used to control levodopa-induced MF in other countries, it has not been considered in the management of PD in Brazil. We report here our initial experience with subcutaneous injections of apomorphine combined to oral domperidone. We administered apomorphine in doses ranging from 1.5 to 3 mg in four PD patients with MF of our outpatient clinic. All the doses administered switched the "off" state to a motor response qualitatively similar to what is seen in the "on" phase induced by levodopa, including the occurrence of dyskinesia. The latency to turn "on" after apomorphine ranged from 7 to 30 minutes and the duration of the response ranged from 60 to 85 minutes. We observed yawning in all four patients, labial paresthesia in one patient and an inspecific unpleasant sensation in another patient. These side effects were not significant in our four patients. Our data show that the use of apomorphine adds a reliable and effective strategy in the management of MF of PD patients.

Antiparkinson Agents↗
PubMed1975

Apomorphine and piribedil in rats: biochemical and pharmacologic studies.

We studied the biochemical and pharmacologic modes of action of piribedil and apomorphine in the rat. Although both drugs have many points in common, they are also different in many of their manifestations. Apomorphine causes high-intensity, short-duration stereotyped behavior; it is distributed within the brain in uneven fashion, the striatum being the area of lowest concentration as measured by fluorometry. Direct stereotactic injection within the dopaminergic mesolimbic system, and particularly the tuberculum olfactorium, produced constant intense responses. All effects of apomorphine can be blocked by pimozide, but propanolol, a beta blocker, only reduces aggression and ferocity, leaving stereotyped behaviors intact. Finally, L-5-HTP tends to reduce aggression, ferocity, and to a lesser extent stereotypy; MIF or piribedil, as well as reserpine, potentiates the stereotyped behaviors induced by apomorphine, whereas L-DOPA usually decreases them. Piribedil, on the other hand, causes low-intensity, long-duration stereotyped behavior. It is distributed within the brain almost uniformly. Most effects of piribedil can be blocked by pimozide, but propanolol blocks only aggression and ferocity, leaving stereotyped behaviors intact. On the other hand, clonidine, an alpha-receptor agonist, blocks stereotyped behaviors induced by piribedil but markedly increases aggression, ferocity, and motor activity. L-5-HTP and L-DOPA have little effect on piribedil-induced manifestations. Reserpine decreases piribedil stereotypy. The main metabolite of piribedil, S 584, had no clear-cut pharmacologic action in our hands at the dosage used. It is concluded that both apomorphine and piribedil produce stereotyped behavior by modifying the physiologic balance between mesolimbic and nigrostriatal dopaminergic systems. The other actions of apomorphine and piribedil upon aggression, ferocity, and motor activity are not always in parallel and depend probably on the fact that piribedil is less specific, affecting also noradrenergic, serotonergic, histaminergic, and/or cholinergic circuits. The usefulness of piribedil against some forms of human tremor and its low-intensity antiakinetic action probably result from this pattern of pharmacologic activity.

Amygdala↗
PubMed1985

Effects of apomorphine enantiomers and of lisuride on 3,4-dihydroxyphenylalanine production in striatal synaptosomes.

The effects of lisuride and of the R(-)- and S(+)-enantiomers of apomorphine were examined on 3,4-dihydroxyphenylalanine (DOPA) production by striatal synaptosomes and by crude, soluble striatal tyrosine hydroxylase. Due to their catechol structure, the enantiomers were almost equally effective in blocking soluble tyrosine hydroxylase (EC 1.14.16.2) (IC50 = 470 and 890 nM for R(-)- and S(+)-apomorphine, respectively), provided incubations were performed at pH 7.2 with 1 mM tetrahydrobiopterin as cofactor. The enantiomers were similarly effective in blocking synaptosomal DOPA production (IC50 = 410 and 970 nM for R(-)- and S(+)-apomorphine, respectively). As S(+)-apomorphine but not R(-)-apomorphine is considered to be a dopamine antagonist, these results support the assumption that the block of synaptosomal DOPA production by both apomorphine enantiomers is due to a direct inhibition of tyrosine hydroxylase. Lisuride at high concentrations (10-100 microM) blocked DOPA production in striatal synaptosomes; simultaneously, intrasynaptosomal dopamine was depleted. These data support the assumption that lisuride inhibits DOPA production indirectly, similar to reserpine. In accordance with this assumption, lisuride was without effect on DOPA production in dopamine-depleted synaptosomes. These results demonstrate that inhibition of synaptosomal DOPA production by at least some dopamine agonists may be explained by direct inhibitory effects on tyrosine hydroxylase.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Characteristics of yawning behavior induced by apomorphine, physostigmine and pilocarpine.

Apomorphine, a dopamine receptor agonist, physostigmine, an anticholinesterase agent and pilocarpine, a cholinergic receptor agonist, produced yawning in rats, with the most effective doses being 0.25 mg/kg, 0.2 mg/kg and 4 mg/kg, respectively. The yawning induced by these drugs is characterized by differences in direction of head moving, tongue protruding and duration of the yawn. The apomorphine-induced yawn was characterized by a slow and wide opening of the mouth with the head moving mainly downward and with a marked protrusion of the tongue. The apomorphine-induced yawn was 3.6 sec in duration. Physostigmine elicited a similar yawn to that seen with apomorphine, except for moving of the head in the upward direction. The pilocarpine-induced yawn was characterized by the head moving forward with a high frequency but without tongue protrusion and lasted 1.8 sec. The frequency of physiological yawning was low, but the behavioral posture was almost similar to that of physostigmine-induced yawning. The characteristics of yawns induced by these agents were unchanged at all doses of the drugs. Different doses altered the frequency of yawning. After pretreatment with mecamylamine, the apomorphine- and physostigmine-induced tongue protruding was inhibited and the duration of the yawning induced by the both drugs was shortened. The results suggest that the behavioral features of yawning induced by apomorphine, physostigmine and pilocarpine differ from one another, and that physiological yawning as well as physostigmine-induced yawning may be mediated by endogenous acetylcholine which stimulates both muscarinic and nicotinic receptors.

Animals↗
PubMed1982

Interrelations between dopaminergic and GABA-ergic transmitter mechanisms in apomorphine stereotypy.

The effects of dopamine (DA)-ergic and GABA-ergic pharmacological agents on apomorphine stereotypy upon intraperitoneal administration in male albino rats has been studied. It has been found that: the DA-ergic agonist L-DOPA increases the intensity of apomorphine stereotypy, without influencing its total duration. The DA-ergic antagonist haloperidol inhibits significantly apomorphine stereotypy, with marked dose-effect dependence, shortening its duration. The GABA-ergic antagonist picrotoxin potentiates nearly twice apomorphine stereotypy and increases its duration. The GABA-ergic agonists depakine and aminooxyacetic acid (AOAA) inhibit substantially apomorphine stereotypy and shorten its duration. Participation of DA-ergic and GABA-ergic transmitter mechanisms in apomorphine stereotypy as well as interactions of these two transmitter systems in the nigrostriatum, are assumed.

Aminooxyacetic Acid↗
PubMed1982

Postpartum exposure to triethyl tin produces long-term alterations in responsiveness to apomorphine.

Male and female rat pups were exposed to a single dose of triethyl tin (TET) or ethanol vehicle on day 5 postnatally and tested for responsiveness to apomorphine as adults. TET-exposed animals displayed an increased response to the stereotypic effects of 1 mg/kg of apomorphine. Female rats exposed neonatally to TET had decreased baseline rates of responding on a food reinforced variable interval (VI) 15 sec. schedule, while TET-exposed males were found to have increased baseline rates relative to controls. The rats maintained on a VI 15 sec. schedule were given various doses of apomorphine (0.0312-0.25 mg/kg, s.c.). Neonatal exposure to TET had no effect on the disruptive effects of apomorphine on VI 15 sec. responding. These data show an altered responsiveness of TET-exposed animals to higher doses of apomorphine (1 mg/kg), but not to lower doses of apomorphine (0.0312-0.25 mg/kg). The present data are in accord with the hypothesis that one of the long-term consequences of neonatal exposure to TET might be an alteration in the responsiveness of the dopamine system.

Animals↗
PubMed1982

Interaction of apomorphine and stressors in the production of hyperthermia in the rabbit.

Apomorphine-induced hyperthermia in the rabbit was shown to be dependent upon the presence of stressors. Two types of stressors were used: 1) a physical stressor, foot shock; and 2) an emotional stressor, conditioned fear. Apomorphine (4 mg/kg i.v.), in the absence of a stressor, produced behavioral responses of arousal, stereotypic gnawing and hind foot thumping. Foot shock, which in control animals exerted no temperature effects, when paired with apomorphine administration, produced a hyperthermic response of 1.3 degrees C. This hyperthermia was abolished by pretreatment with diazepam (5 mg/kg i.v.) or haloperidol (50 micrograms/kg i.v.). Classical conditioning was used to provide the emotional stressor and was accomplished by pairing a tone with foot shock. After conditioning the tone combined with apomorphine produced an increase in temperature of 1.3 degrees C, whereas the tone paired with saline (1 ml/kg i.v.) produced no hyperthermia. An intensity vs. effect curve was determined, and foot shock alone elicited increases of temperature in a dose-dependent manner. At a given shock intensity, apomorphine elicited a much greater response than shock alone and also decreased the threshold for response to shock. Our findings firmly establish the hypothesis that apomorphine elicits hyperthermia in the presence of stressors by increasing sensitivity and decreasing the threshold for response to stressors.

Animals↗
PubMed1980

Blood pressure and heart rate response to apomorphine in urethane anesthetized rats.

The mechanisms involved in the hypotensive effect of apomorphine were studied in urethane anesthetized rats. The intravenous injection of apomorphine (0.01-0.75 mg/kg) produced a dose dependent fall in mean blood pressure. At the higher doses used (0.5-0.75 mg/kg) a marked bradycardia accompanied the hypotensive effect. These cardiovascular effects were prevented by pretreating the animals with pimozide (0.01-0.1 mg/kg). Low doses of haloperidol (0.03-0.3 mg/kg) did not antagonize the hypotensive action of apomorphine. Higher doses of haloperidol (1-3 mg/kg) reduced markedly the mean blood pressure. Atropine (1 mg/kg) partially antagonized the decrease in mean blood pressure induced by apomorphine and prevented completely the bradycardia. Hexamethonium (10 mg/kg) reduced the mean blood pressure and when apomorphine was administered, a residual hypotensive effect and no bradycardia was observed. It is concluded that the cardiovascular actions of apomorphine are central in origin and mainly due to the stimulation of a dopamine receptor. A probable peripheral effect could not be discarded.

Animals↗
PubMed1993

[Apomorphine test in Parkinson disease--dose and corresponding parameters].

The apomorphine test is a well known indicator of therapeutic responsiveness to dopaminergic substances and a reliable instrument for the differential diagnosis of idiopathic Parkinson's disease. The relationship between apomorphine dosage and the following parameters, namely age, duration of disease, body height, body surface, skinfold thickness of the abdominal wall and the upper arm as a measure of subcutaneous fatty tissue, and amount of administered L-dopa was studied in 45 patients with Parkinson's disease in whom the apomorphine test was positive. In addition we investigated whether different doses of apomorphine resulted in significant differences of the parameters studied. The determined parameters correlated with the given dose of apomorphine (p < 0.05) and thus, represent a potential indicator for optimal L-dopa dose determination and intermittent or continuous apomorphine administration.

Adult↗
PubMed1995

[Apomorphine test: evaluation of dopaminergic response in patients with Parkinson disease].

Apomorphine is a potent dopaminergic agonist that quickly and predictably reverts parkinsonian symptomatology. In 32 patients (18 male) aged 45 to 83 years old (22 with idiopathic parkinsonism and 10 with parkinsonism of other causes), the dopaminergic response to apomorphine after domperidone administration was assessed using the digital skill test and Webster scale. Twenty patients with idiopathic parkinsonism and 1 with parkinsonism of other causes had a positive response to apomorphine. In 44% apomorphine had adverse effects. All patients with idiopathic parkinsonism and the only patient with parkinsonism of other causes with a positive apomorphine test had a good response to levodopa therapy. It is concluded that apomorphine test has a 95% positive predictive value for idiopathic parkinsonism and is a useful diagnostic tool.

Aged↗
PubMed1995

Sublingual apomorphine: a new pharmacological approach in Parkinson's disease?

Apomorphine, a potent dopamine agonist with mixed D1 and D2 properties, has long been recognized to have antiparkinsonian effect. Its oral administration is limited by both its hepatic first pass metabolism and adverse side effects (nausea, vomiting, azotemia). It is now widely used by subcutaneous route for the treatment of severe "off" periods seen with levodopa treatment. However, the use of penjects can be difficult in some patients with severe tremor or akineto-rigid symptoms during "off" periods. Our group has recently investigated the effect of sublingual administration of apomorphine in patients suffering from Parkinson's disease. Sublingual apomorphine was shown to reduce extrapyramidal symptoms. The main characteristics of the pharmacodynamic effects of sublingual apomorphine in parkinsonians and the relationship between pharmacodynamic and pharmacokinetic effects are discussed. Sublingual apomorphine has the advantage of being easier to administer than subcutaneous injection. For the moment, the long-term use of sublingual apomorphine is limited by two major problems: first, time for dissolution and switch "on" (which is longer than after subcutaneous route) and secondly, the occurrence of local side effects (stomatitis). Further clinical studies using either more efficient (tablets with faster dissolution) and better tolerated sublingual formulations or other dopamine agonists should be carried on before recommending this approach in the treatment of Parkinson's disease.

Administration, Sublingual↗
PubMed1997

Apomorphine modifies the visual responses of cells in the rabbit's lateral geniculate nucleus.

It has been shown that enhancing or reducing dopaminergic activity in the retina modifies the balance between center and surround responses of retinal neurons such as ganglion cells. We investigated how these changes are reflected in the dorsal lateral geniculate nucleus (dLGN) by studying the effects of injections of apomorphine, a mixed D1 and D2 agonist of dopamine, on the visual responses of geniculate cells. Experiments were carried out on anesthetized adult pigmented rabbits. A varnished tungsten microelectrode was used to record single-unit activity in the dLGN. The flash electroretinogram was also recorded to monitor retinal changes and to confirm the success of the injections. Apomorphine was injected intravitreally or intravenously. The results can be summarized as follows. Apomorphine decreased the amplitude of the b-wave of the electroretinogram. For most dLGN cells, apomorphine produced a strong reduction in response amplitude evoked by sine-wave grating stimuli, presented at various spatial frequencies. Responses to flashing spots were also reduced but to a much lesser extent than those to gratings. In addition, the balance between the responses to small and large spots changed in favor of large stimuli. Consequently, after injection of apomorphine, the geniculate cells were preferentially activated by large-sized flashing stimuli. These data suggest that apomorphine can reduce the spatial contrast sensitivity of cells in the dLGN. This effect could be mediated by the reduction of the strength of lateral inhibition at the retinal level.

Animals↗
PubMed1976

Changes in sensitivity to apomorphine during morphine dependence and withdrawal in rats.

Stereotyped behavior induced by injection of apomorphine hydrochloride (10 mg/kg i.p) was measured in control rats, rats made dependent on morphine and dependent rats undergoing naloxone-precipitated withdrawal. The dose of apomorphine chosen was approximately the ED50 dose, so that changes in sensitivity to apomorphine in either direction could be determined. Rats which had received a subcutaneous morphine (75 mg) pellet implant 72 hours previously demonstrated an increased sensitivity to apomorphine when compared with placebo-implanted controls. During withdrawal precipitated by injection of naloxone hydrochloride (0.2 mg/kg i.p.) this increased sensitivity disappeared. Naloxone alone, in a dose of 1.0 mg/kg but not 0.2 mg/kg, significantly antagonized apomorphine-induced stereotyped behavior and these effects of apomorphine were also reduced by an acute injection of morphine sulfate (10 mg/kg). The significance of these findings with regard to changes in central dopaminergic systems during dependence and withdrawal is discussed.

Animals↗
PubMedDate not supplied

Stepwise intravenous infusion of apomorphine to determine the therapeutic window in patients with Parkinson's disease.

A new experimental strategy was applied to determine the concentration-effect relation and the therapeutic window of apomorphine in individual patients with Parkinson's disease. Apomorphine was administered by a stepwise intravenous infusion. The infusion rate was increased by 10 micrograms/kg/h every 20 minutes, up to 100 micrograms/kg/h or less when adverse effects occurred. Thereafter, the infusion rate was decreased in a stepwise fashion until zero. Plasma apomorphine concentrations were measured every 20 minutes. Clinical efficacy (tapping score and tremor), dyskinesia, and adverse effects were monitored at the same time. The mean clearance of apomorphine was 4.5 L/min (2.2 to 6.6 L/min). Of the 10 patients, 8 responded to apomorphine. The effects were quantal rather than continuous. Within each patient, the concentrations at onset and offset of effect generally were similar. Significant interpatient variability was observed with respect to minimal concentration for each of the effects. Clinical efficacy occurred at a mean minimal effective concentration (MEC) of 4.7 ng/mL (range 1.4 to 10.7 ng/mL). Dyskinesia was observed at a mean concentration of 8.5 ng/mL (range 2.7 to 20 ng/mL). This value was not significantly different from the MEC. The mean minimal toxic concentration was 16.7 ng/mL (8.5 to 24.5 ng/mL) and was significantly different from the mean MEC. In conclusion, the stepwise increase and decrease of the intravenous infusion rate is a suitable tool for the establishment of the concentration-effect relation of apomorphine in individual patients. The finding of a narrow therapeutic window, in which the onset concentrations vary from patient to patient, underlines the need for accurate and individualized dosing.

Adult↗
PubMed2000

Effects of clonidine and alpha-adrenoceptor antagonists on motor activity in DSP4-treated mice II: interactions with apomorphine.

Adult mice were administered either the noradrenaline (NA) neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) or distilled water (control), 10-12 days before motor activity testing, and 6 h before testing all the mice were administered reserpine (10 mg/kg), the monoamine-depleting agent. The interactive effects of (I) clonidine, the alpha(2)-adrenoceptor agonist, with the dopamine (DA) agonist, apomorphine, and the alpha(2)-antagonist, yohimbine, and (II) with either yohimbine or the alpha(1)-antagonist, prazosin, upon motor behaviour in activity test chambers were studied in reserpinized DSP4-treated and control mice. It was shown that apomorphine (3 mg/kg) increased locomotor and total activity in both reserpinized DSP4-treated and control mice but the effect was attenuated in the DSP4 mice. Co-administration of clonidine (3 mg/kg) with apomorphine potentiated the effects of apomorphine on motor activity and this effect was enhanced markedly by DSP4 pretreatment. Yohimbine (10 mg/kg) antagonized the motor activity-stimulating effects of apomorphine in both DSP4-treated and control mice. Co-administration of clonidine with apomorphine, following yohimbine, restored motor activity levels to those obtained in the absence of yohimbine and this effect upon locomotor activity was enhanced by DSP4 pretreatment. The effects of clonidine on motor activity were enhanced by NA-denervation. Prazzosin (3 mg/kg) enhanced the locomotor activity of both reserpinized DSP4-treated and control mice after the initial 30-min period but was not affected by DSP4 treatment. Analysis of post-decapitation convulsions (PDCs) indicated loss of the reflex by DSP4 pretreatment. Reserpine pretreatment abolished the initial, exploratory phase (30 min) of motor activity. These results demonstrate interactions between NA and DA systems that may bear eventual relevance to neurologic disorders such as parkinsonism.

Journal Article↗
PubMed1997

Effects of intrastriatal infusion of D2 receptor antisense oligonucleotide on apomorphine-induced behaviors in the rat.

An antisense oligonucleotide strategy was employed to specifically deplete postsynaptic striatal D2 receptors in order to determine the possible role of presynaptic D2 autoreceptors in mediating behavioral responses induced by low doses of apomorphine. A phosphorothioate-modified antisense oligonucleotide complementary to the first 19 bases of the coding region of D2 receptor mRNA, a scrambled sequence comprising the same bases, or saline was infused bilaterally into the striatum of adult rats, twice daily for 2 days via indwelling cannulae. After an interval of 8-12 h, rats were habituated and challenged with high (300 micrograms/kg; subcutaneous) or low (50 micrograms/kg; s.c.) doses of apomorphine or its vehicle (0.1% ascorbic acid). Yawning, vacuous chewing mouth movements, hypoexploration, and penile grooming induced by low-dose apomorphine were unaffected by antisense infusion into the striatum, whereas stereotypic sniffing following high-dose apomorphine was markedly suppressed. Intrastriatal infusion of antisense resulted in significantly diminished [3H]-raclopride binding, while binding of [3H]-SCH 23390 (D1 receptors) and [3H]-WIN 35428 (dopamine transporter) was unchanged. D2 mRNA levels determined by quantitative in situ hybridization were normal in the striatum and the substantia nigra. Our results confirm that stereotypic sniffing is mediated via postsynaptic D2 receptors in the striatum, and favor the notion that behavioral responses induced by low doses of apomorphine are mediated by presynaptic D2 autoreceptors.

Animals↗
PubMed1999

Subthalamic responses to amphetamine and apomorphine in the behaving rat with a unilateral 6-OHDA lesion in the substantia nigra.

The activity of neurons in the subthalamic nucleus (STN) of the behaving rat, before and after a unilateral 6-OHDA lesion of the substantia nigra, was recorded with the extracellular technique to determine whether it was altered following systemic amphetamine, 5 mg/kg, apomorphine, 3 mg/kg, and apomorphine, 0.3 mg/kg, and whether in cases of altered activity, it was related to the drug-induced motor response expressed concurrently. Activity in the STN of intact rats increased dramatically after amphetamine, 5 mg/kg. This excitatory response had the same latency, similar magnitude, and the same duration as the motor response expressed in terms of locomotion and oral stereotypy. Motor and unit responses were also induced by amphetamine after the lesion with 6-hydroxydopamine (6-OHDA), but now the excitatory response was attenuated while the motor response was not. The effects of the 6-OHDA lesion were the same in all animals with loss of the nigra dopamine neurons, regardless of whether they were rotators or non-rotators. Activity in the STN of intact rats also increased after apomorphine, 3 mg/kg, and again, this increase was correlated with the increase in motor behavior, but both responses were of shorter duration than the responses to amphetamine. The increases in unit activity and motor behavior induced by apomorphine in the 6-OHDA-lesioned rats had the same magnitude but lasted longer than in the intact rats. Treatment with apomorphine, 0.3 mg/kg, of the intact rats produced small and very brief increases in the activity of the STN and in motor behavior. The same treatment given the 6-OHDA-lesioned rats produced responses of larger magnitude but no change in duration. These findings demonstrate a role for STN neurons in the mediation of the motor behaviors induced by stimulation of the dopamine receptor. The results also show that a unilateral lesion of the substantia nigra with 6-OHDA did not block these responses but altered them in a manner consistent with a dopaminergic deafferentation of the basal ganglia. The increased activity in the STN during the expression of dopamine-dependent motor behavior conflicts with the current model of basal ganglia function that assumes prejudicial effects of excessive STN activity on the expression of motor behavior. An explanation for this conflict suggests that it is more apparent than real.

Action Potentials↗