Administration Of Reserpine Research Articles

Altered expression of regulators of G-protein signaling (RGS) mRNAs in the striatum of rats undergoing dopamine depletion

Quantitative in situ hybridization was used to investigate the effect of prolonged striatal dopamine or monoamine depletion on the mRNA density of regulators of G-protein signaling (RGS) 2–12 proteins. Two types of treatments were studied: a 6-hydroxydopamine-induced unilateral lesion of the nigrostriatal pathway and a 5-day reserpine treatment. The results clearly show a selective increase in the mRNA levels of RGS2, 5 and 8 and a decrease in RGS4 and 9 mRNA levels following nigrostriatal denervation. In this model, we observed no change in the mRNA levels of RGS10 and other RGS proteins that are weakly expressed in the striatum (RGS3, 6, 7, 11 and 12). On the other hand, the mRNA levels RGS2, 4, 5, 8, 9 and 10 were found to be significantly decreased after prolonged reserpine treatment. In contrast, the densities of these transcripts (in particular, RGS2, 4 and 10) tend to increase after an acute administration of reserpine, used as control. These results provide further evidence for the influence of dopamine and/or other monoamines in the regulation of RGS protein expression in the striatum. In connection with the previously documented acute regulation of RGS proteins after modulation of the dopaminergic transmission [Geurts et al., Neurosci Lett 2002;333:146–50], the present study demonstrates that alteration in their genetic expression can be long-lasting and this could reflect the adaptation processes that occur in certain pathological states, such as Parkinson’s disease.

Antidyskinetic effects of risperidone on animal models of tardive dyskinesia in mice

The effects of risperidone, an atypical neuroleptic, were investigated on two animal models of tardive dyskinesia (TD). The repeated administration of reserpine (1.0 mg/kg) or haloperidol (2.0 mg/kg) induces orofacial movements in mice, which are very similar to those observed in humans presenting TD. The effects of acute or repeated treatment with several doses of risperidone (0.1; 0.5; 2.0 or 4.0) on the expression and development of orofacial movements in reserpine- and haloperidol-treated male mice were investigated. The results showed that risperidone per se did not induce the development of orofacial movements. In addition, this drug was able to attenuate the expression and the development of reserpine—as well as haloperidol-induced orofacial movements. These results are in line with several clinical studies that suggest not only a lower incidence of TD in schizophrenic patients treated with risperidone, but also an antidyskinetic effect of this drug in patients previously treated with classical neuroleptics.

Ebselen attenuates reserpine-induced orofacial dyskinesia and oxidative stress in rat striatum

Reserpine-induced orofacial dyskinesia is an alleged animal model of tardive dyskinesia whose pathophysiology has been related to striatal oxidative stress. In the present investigation, the authors examined whether ebselen, an antioxidant organochalcogen with glutathione peroxidase-like activity, changes the behavioral and neurochemical effect of acute reserpine administration. Reserpine injection for 3 days every other day caused a significant increase on the tongue protrusion frequency and ebselen (30 mg/kg ip for 4 days, starting 1 day before reserpine) reversed partially the effect of reserpine ( P<.05). Reserpine- and reserpine+ebselen-treated groups displayed an increase in vacuous chewing frequency when compared to control and ebselen-treated groups ( P<.05) Reserpine increased the duration of facial twitching and ebselen reversed partially the effect of reserpine ( P<.01). Reserpine increased significantly the thiobarbituric acid-reactive species (TBARS) levels, and ebselen reversed the effect of reserpine on TBARS production in rat striatum. The results of the present study clearly indicated that ebselen has a protective role against reserpine-induced orofacial dyskinesia and reversed the increase in TBARS production caused by reserpine administration. Consequently, the use of ebselen as a therapeutic agent for the treatment of tardive dyskinesia should be considered.

Inhibitory effect of reserpine on dopamine transporter function

Previous studies indicate that reserpine may disrupt dopamine transporter activity. Results presented herein reveal that it also inhibits potently synaptosomal [ 3H]dopamine uptake. In addition, reserpine administration to rats decreased the V max of synaptosomal dopamine transport, as assessed ex vivo 12 h after treatment. This decrease appeared, at least in part, dissociated from concurrent inhibition of the vesicular monoamine transporter-2 (VMAT-2). In separate experiments, synaptosomal dopamine uptake did not differ between wild-type and heterozygous VMAT-2 knockout mice, and reserpine treatment did not inhibit [ 3H]dopamine uptake into cells heterogously expressing the human dopamine transporter. Taken together, these data suggest that reserpine may transiently alter dopamine transporter function in a noncompetitive, indirect manner.

Evaluation of the face validity of reserpine administration as an animal model of depression–Parkinson's disease association

The aim of the present study was to develop an animal model for the study of depressive symptoms associated with Parkinson's disease (PD). Mice treated intraperitoneally with reserpine (RES), 2.0 and 1.0 mg/kg, or its vehicle (VEHIC) were submitted to the sucrose solution (2%) consumption test (a model employed to mimic the depressive symptoms found in PD) and to the spontaneous locomotor activity test (a model employed to mimic the motor impairment found in PD). All animals were submitted to both tests. Twenty-four hours after treatment, only RES 2.0-treated animals showed a significantly decreased preference for the sucrose solution (mean±S.E.M. RES 2.0=54.4±4.1%, RES 1.0=68.5±2.5%, VEHIC=62.3±4.1%). There was no significant difference among groups in water, sucrose or total fluid consumption. Locomotor activity was significantly decreased by both RES doses (number of beam interruptions: RES 2.0=59.9±11.4, RES 1.0=82.2±9.7, VEHIC=116.8±8.2). Thus, RES 2.0 administration to mice induced depressive (anhedonia) and motor (decreased locomotor activity) symptoms of depression–PD association. This suggests that the RES model shows an important aspect of face validity for the depressive state associated with PD, i.e., phenomenological similarities between the model and the situation being modeled.

Effects of cocaine and reserpine administration on RNA editing of rat 5-HT2C receptor estimated by primer extension combined with denaturing high-performance liquid chromatography.

Serotonin 2C receptor (5-HT(2C)R) transcripts undergo RNA editing, generating pharmacologically different isoforms. To test whether the RNA editing of 5-HT(2C)R is regulated by serotonergic activity, effects of cocaine or reserpine administration in the rat cerebral cortex were examined. Although these drugs have been known to alter serotonin metabolism, no alterations in the RNA editing were found by the sequencing analysis. Towards high throughput analysis, we developed a non-RI method that allows accurate and rapid estimation of RNA editing by combining the primer extension with denaturing high-performance liquid chromatography (DHPLC). By using this, RNA editing efficiencies of 5-HT(2C)R in the midbrain and hippocampus as well as the cerebral cortex were examined, and no alterations were found among these regions. Our method using DHPLC is applicable to examine association of RNA editing with various diseases.

Alpha-1 adrenoceptor up-regulation induced by prazosin but not KMD-3213 or reserpine in rats.

1. We have investigated the effects of chronic administration of prazosin (a subtype-nonspecific alpha-1 AR antagonist), KMD-3213 (an alpha-1A AR subtype-specific antagonist) and reserpine (a catecholamine depletor) on the density of alpha-1 AR subtypes in various rat tissues (liver, kidney, submaxillary gland, heart and spleen). 2. Administration of prazosin (2 mg kg(-1) day(-1), i.p.) for 2 weeks did not affect K(D) values for [(3)H]-prazosin or [(3)H]-KMD-3213 of alpha-1 ARs in five rat tissues tested. However, it caused 52% up-regulation of alpha-1B AR in the spleen, and 84% and 107% up-regulation of alpha-1A- and alpha-1B ARs, respectively, in the heart. Although major subtypes of alpha-1 AR are alpha-1A AR in the submaxillary gland, alpha-1B AR in the liver, and alpha-1A and alpha-1B ARs in the kidney, these tissues showed no up-regulation. The mRNA levels of alpha-1 AR subtypes were not affected by prazosin administration in any tissue tested. 3. Neither administration of KMD-3213 (2 mg kg(-1) day(-1), i.p.) nor reserpine (0.5 - 1 mg kg(-1) day(-1), i.p.) for 2 weeks caused any change in either the binding affinity for [(3)H]-prazosin or [(3)H]-KMD-3213 or the density of the alpha-1 AR subtypes in the five rat tissues. 4. Neither prazosin nor KMD-3213 treatment reduced the noradrenaline content in the five rat tissues, in contrast to reserpine treatment, which markedly reduced it. 5. The findings of the present study demonstrated that up-regulation of alpha-1 AR is selectively caused by prazosin treatment in some tissues but neither by KMD-3213 treatment nor by chemical denervation with reserpine. These results suggest that up-regulation of alpha-1 ARs is not caused by a simple blockade of sympathetic tone.

Concomitant development of oral dyskinesia and memory deficits in reserpine-treated male and female mice

It has been suggested that reserpine-induced oral dyskinesia in rats may provide a new animal model of tardive dyskinesia. Both cognitive deficits and gender have been associated with the development of tardive dyskinesia. The aim of the present study was to investigate the effects of reserpine administration on the development of orofacial dyskinesia and on plus-maze discriminative avoidance task (DAT—an animal model of associative learning) in male and female mice. Male and female mice received 1.0 mg/kg reserpine or saline subcutaneously on day 1. On days 3, 6 and 8, the frequency of vacuous chewing movements (VCM) was quantified. On day 6, the DAT conditioning was performed, in a modified elevated plus-maze. In one of the enclosed arms, the animals received aversive stimulation (light and noise). On day 8, a test session was performed and the time spent by the animals in each of the enclosed arms was recorded. Our results showed that reserpine-treated male and female mice presented significantly higher VCM when compared with respective control groups in all observation days. On day 6, reserpine-treated female mice presented significantly higher VCM when compared with male mice injected with this drug. The DAT test performed on day 8 showed that the time spent in the aversive arm by saline-treated mice was significantly lower than the time spent in the non-aversive arm. This difference was not observed for reserpine-treated mice. Our results demonstrate the development of reserpine-induced oral dyskinesia in both male and female mice. While this oral dyskinesia is accompanied by a cognitive deficit in both genders, female mice tended to have more severe oral dyskinesia. It is suggested that reserpine-induced oral dyskinesia may provide a quick, simple and efficient mouse model of tardive dyskinesia.

Reserpine or chronic paroxetine treatments do not modify the vesicular monoamine transporter 2 expression in serotonin-containing regions of the rat brain

To date, very little information is available about the regulation of vesicular monoamine transporter in central serotonergic regions. The expression of the vesicular monoamine transporter 2 (VMAT2) has been studied in the serotonergic system of the rat brain after an 18 day treatment with the serotonin selective-reuptake inhibitor paroxetine (10 mg/kg, i.p., once daily). This treatment, while increasing serotonergic transmission, did not modify either VMAT2 mRNA expression or 3H-dihydrotetrabenazine binding site density in any of the studied regions. These results suggest that VMAT2 regulation in the central serotonergic system is not involved in the mechanism of action of antidepressants. In addition, a single administration of reserpine (5 mg/kg, s.c.), while blocking the vesicular monoamine uptake function, had no effect on VMAT2 immunoreactivity in the dorsal raphe nucleus 2 or 30 days after injection. It is concluded that neither a reduction (reserpine) nor an enhancement (paroxetine) of the serotonin transmission induces VMAT2 regulation in serotonergic system in the rat brain.

Gastric mucosal lesions induced by complete dopamine system failure in rats. The effects of dopamine agents, ranitidine, atropine, omeprazole and pentadecapeptide BPC 157

Up to now, for gastric lesions potentiation or induction, as well as determination of endogenous dopamine significance, dopamine antagonist or dopamine vesicle depletor were given separately. Therefore, without combination studies, the evidence for dopamine significance remains split on either blockade of dopamine post-synaptic receptor or inhibition of dopamine storage, essentially contrasting with endogenous circumstances, where both functions could be simultaneously disturbed. For this purpose, a co-administration of reserpine and haloperidol, a dopamine granule depletor combined with a dopamine antagonist with pronounced ulcerogenic effect, was tested, and the rats were sacrificed 24 h after injurious agent(s) administration. Haloperidol (5 mg.kg –1 b.w. i.p.), given alone, produced the lesions in all rats. Reserpine (5 mg.kg –1 b.w. i.p.), given separately, also produced lesions. When these agents were given together, the lesions were apparently larger than in the groups injured with separate administration of either haloperidol or reserpine alone. Along with our previous results, when beneficial agents were co-administered, all dopaminomimetics (bromocriptine 10 mg, apomophine 1 mg, amphetamine 20 mg.kg –1 i.p.) apparently attenuated the otherwise consistent haloperidol-gastric lesions. Likewise, an apparent inhibition of the reserpine-lesions was noted as well. However, if they were given in rats injured with combination of haloperidol and reserpine, their otherwise prominent beneficial effects were absent. Ranitidine (10 mg), omeprazole (10 mg), atropine (10 mg), pentadecapeptide BPC 157 (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) (10 μg or 10 ng.kg –1 i.p.) evidently prevented both haloperidol-gastric lesions and reserpine-gastric lesions. Confronted with potentiated lesions following a combination of haloperidol and reserpine, these agents maintained their beneficial effects, noted in the rats treated with either haloperidol or reserpine alone. The failure of dopaminomimetics could be most likely due to more extensive inhibition of endogenous dopamine system activity, and need for remained endogenous dopamine for their salutary effect, whereas the beneficial activities of ranitidine, omeprazole, atropine, pentadecapeptide BPC 157 following dopamine system inhibition by haloperidol+reserpine suggest their corresponding systems parallel those of dopamine system, and they may function despite extensive inhibition of endogenous dopamine system activity.

The role of the sympathetic nervous system in radiation-induced apoptosis in jejunal crypt cells of spontaneously hypertensive rats.

To evaluate the effect of the sympathetic nervous system on radiation-induced apoptosis in jejunal crypt cells, apoptosis levels were compared in spontaneously hypertensive rats (SHR), animals which are a genetic hyperfunction model of the sympathetic nervous system, and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were exposed to whole body X-ray irradiation at doses from 0.5 to 2 Gy. The apoptotic index in jejunal crypt cells was significantly greater in SHR than in WKY at each time point after irradiation and at each dose. WKY and SHR were treated with reserpine to induce sympathetic dysfunction, and were subsequently exposed to irradiation. Reserpine administration to SHR or WKY resulted in a significant suppression of apoptosis. p53 accumulation was detected in the jejunum in both WKY and SHR after irradiation by Western blotting analysis. There were no significant differences in the levels of p53 accumulation in irradiated intestine between WKY and SHR. These findings suggested that hyperfunction of the sympathetic nervous system is involved in the mechanism of high susceptibility to radiation-induced apoptosis of the jejunal crypt cells.

A PET study of D(1)-like dopamine receptor ligand binding during altered endogenous dopamine levels in the primate brain.

Several positron emission tomography (PET) studies have shown that radioligand binding to D(2)-like dopamine receptors competes with endogenous dopamine. The purpose of this PET study was to examine the effect of amphetamine and reserpine on D(1)-like dopamine receptor binding. Three Cynomolgus monkeys were examined with the radioligands [(11)C]SCH 23390 or [(11)C]NNC 112 at baseline condition and after pretreatment with amphetamine (2 mg/kg IV). The B/F values (binding potential) in the striatum and the neocortex were calculated at transient equilibrium. In two monkeys, the effect of the long-lasting dopamine depletion after reserpine (1 mg/kg IV) was followed by a repeated Scatchard procedure in up to 77 days after drug administration. The Scatchard analysis was based on two PET measurements with high and low specific radioactivity and allowed the calculation of D(1)-like dopamine receptor density (B(max)) and apparent affinity (K(D)(app)). The effect of amphetamine on the B/F values was between -14 and 6%. These changes can be considered as within the range of the test-retest reliability. Thus, there was no evident effect of amphetamine-induced dopamine release on D(1)-like dopamine receptor binding. Five hours after reserpine administration, there was no change in B(max) or K(D)(app). At 3, 23, and 28 days after reserpine administration, the Scatchard analyses indicated a 13-20% reduction in B(max) without any evident change in K(D)(app) in both the striatum and the neocortex. The lack of evident effects of amphetamine and reserpine on D(1)-like dopamine receptor binding is markedly different from the 20% amphetamine-induced decrease and 50% reserpine-induced increase that has been consistently reported for D(2)-like dopamine receptor binding. The data indicated that D(1)-like dopamine receptor occupancy of endogenous dopamine is low at physiological condition. It is thus unlikely that D(1)-like dopamine receptor radioligands can be used to measure changes in the concentration of endogenous dopamine.

Locomotor activity and accumbens Fos expression driven by ventral hippocampal stimulation require D 1 and D 2 receptors

Numerous studies have suggested that excitatory projections from the ventral hippocampus to the nucleus accumbens modulate locomotor activity in rats. Furthermore, the ability of ventral hippocampal neurons to alter locomotor activity may involve the dense dopaminergic innervation found in the nucleus accumbens. The purpose of this study was to: (i) more fully characterize the locomotor effects of acute alterations in ventral hippocampal activity; (ii) ascertain the influence of dopamine agonists and antagonists on locomotor changes produced by altered ventral hippocampal activity; and (iii) use immediate early gene induction to determine whether dopamine antagonists alter the response of nucleus accumbens neurons to ventral hippocampal stimulation. By comparing a variety of excitatory amino acid agonists, it was found that ventral hippocampal infusion of N-methyl- d-aspartate elevated locomotor activity in a subconvulsive manner, while other excitatory amino acid receptor agonists did not. Inactivation of the ventral hippocampus achieved by lidocaine infusion did not suppress ongoing locomotor activity, nor did it affect amphetamine-induced increases in locomotor activity. Increases in locomotor activity induced by ventral hippocampal N-methyl- d-aspartate infusion were blocked by systemic administration of haloperidol (a D 2 receptor antagonist), SCH-23390 (a D 1 receptor antagonist) or reserpine. Cellular expression of the protein product of the immediate early gene, c-fos, was dramatically increased in the nucleus accumbens shell after ventral hippocampal N-methyl- d-aspartate infusion, and haloperidol, SCH-23390 and reserpine attenuated this effect. These results suggest that the increases, but not decreases, in ventral hippocampal activity have a measurable effect on ongoing rates of locomotion, and that this effect requires both D 1 and D 2 receptors. Moreover, the studies of Fos expression suggest that dopamine receptor antagonists attenuate neuronal responses to ventral hippocampal stimulation within the nucleus accumbens, a brain region important in the generation and maintenance of locomotor activity.

ATP as a source of interstitial adenosine in the rat heart

The contribution of neuronal ATP to interstitial adenosine levels was investigated in isolated perfused rat hearts. Ventricular surface transudates, representing interstitial fluid, were analyzed for norepinephrine, ATP, and adenosine. Exocytotic release of norepinephrine was induced by electrical stimulation of cardiac efferents emanating from the stellate ganglion. Ganglion stimulation increased contractility, interstitial norepinephrine, ATP, and adenosine. Interstitial adenosine was 11- to 27-fold higher than interstitial ATP, suggesting that the released ATP is unlikely the only source of adenosine. In the presence of AOPCP (alpha,beta-methyleneadenosine 5'-diphosphate), an ecto-5'-nucleotidase inhibitor, the ganglion-stimulated increase in interstitial ATP and adenosine reached levels similar to those in the absence of AOPCP, also suggesting that adenosine does not derive from extracellular ATP. The perfusate Ca2+ was raised from 1 to 4 mM to determine the importance of the enhanced contractile function on the levels of norepinephrine, ATP, and adenosine. The results were increases in contractility and interstitial norepinephrine, ATP, and adenosine, which were not suppressed with atenolol, indicating a norepinephrine-independent release of ATP and adenosine. Reserpine treatment and administration of guanethidine depleted the catecholamine stores and diminished the catecholamine release, respectively. However, neither agent altered Ca2+-induced increases in ATP and adenosine. It is concluded that the amount of neuronal-derived ATP is low and most likely does not contribute significantly to interstitial levels of adenosine. Furthermore, elevations in interstitial norepinephrine, ATP, and adenosine are associated with neuronal-independent increases in contractile function.

Effects of Epinephrine on Ouabain-Sensitive, K+-DependentP-Nitrophenylphosphatase Activity in Strial Marginal Cells of Guinea Pigs

In strial marginal cells, Na+/K(+)-ATPase activity is abundant, and contributes to maintain the characteristic electrolyte composition of the cochlear endolymph. In the present study, to clarify the relationship between epinephrine and strial Na+/K(+)-ATPase activity, the ouabain-sensitive, K+-dependent p-nitrophenylphosphatase (K(+)-NPPase) activity of strial marginal cells was investigated with a cerium-based method in normal guinea pigs and guinea pigs treated with reserpine, epinephrine, and reserpine plus epinephrine. In our previous study, K(+)-NPPase activity had almost completely decreased 3 to 20 days after reserpine administration. In the present study, at 10 days after reserpinization and following repeated epinephrine treatment, enzyme activity was detectable. These results suggest that exogenous epinephrine was able to restore strial K(+)-NPPase activity in the reserpine-treated animals, and that epinephrine might increase strial Na+/K(+)-ATPase activity.

Role of NMDA glutamate receptors in regulating D2 dopamine-dependent Fos induction in the rat striatopallidal pathway

Acute administration of reserpine induces Fos expression in striatopallidal neurons, an effect blocked by pretreatment with the D2 dopamine agonist quinpirole. Pretreatment with the NMDA antagonists (+)MK-801 or CPP attenuated reserpine-mediated striatal Fos induction whereas pretreatment with ketamine or the inactive isomer (−)MK-801 did not. These results support a role of NMDA glutamate receptors in regulating the activity of the striatopallidal pathway.

The effect of methamphetamine on the release of acetylcholine in the rat striatum

We examined the effect of methamphetamine on the release of acetylcholine in the striatum of freely moving rats, using an in vivo microdialysis method. The basal level of acetylcholine was 3.67±0.47 pmol/30 μl per 15 min in the presence of neostigmine (10 μM). Tetrodotoxin (1 μM), a selective blocker of voltage-dependent Na + channels, markedly inhibited the release of acetylcholine in the striatal perfusates. Apomorphine (1.0 mg/kg, i.p.), a dopamine receptor agonist, also significantly attenuated acetylcholine release. Methamphetamine (0.1 and 0.5 mg/kg, i.p.) did not immediately affect acetylcholine release in the striatum, but a dose of 1.0 mg/kg (i.p.) induced an increase of acetylcholine release in the striatum at 15–60 min. Striatal infusion of methamphetamine (5 and 10 μM) did not influence acetylcholine release. The increase following intraperitoneal administration of methamphetamine was slightly diminished by haloperidol (0.5 mg/kg). After microinjection of the neurotoxin, 6-hydroxydopamine (6 μg/3 μl), in the substantia nigra 7 days before, the increase of acetylcholine induced by the administration of methamphetamine (1.0 mg/kg) was slightly attenuated, whereas the administration of reserpine (2 mg/kg, i.p.) 24 h before, combined with α-methyl- p-tyrosine (300 mg/kg, i.p.) 2.5 h before, completely blocked the increase in release of acetylcholine. These findings suggest that methamphetamine exerts an excitatory influence on striatal acetylcholine release in freely moving rats, and that this excitatory effect involves the dopaminergic system and the catecholaminergic system.

Reserpine modulates serotonin transporter mRNA levels in the rat brain

Despite recent advances in determining central serotonin (5-HT) function, the basic aspects by which serotonin neurotransmission is controlled and regulated are still not understood. Since the serotonin transporter (5-HTT) is involved in terminating the action of 5-HT that is released from the presynaptic nerve terminal, the regulation of 5-HTT may be an important step in controlling 5-HT neurotransmission at the synaptic cleft. The present study investigated the effects of reserpine administration on 5-HTT gene expression as well as on tryptophan hydroxylase (TPH) expression in the rat brain. Male Sprague-Dawley rats were injected with reserpine (10 mg kg , i.p.) and sacrificed at 8 h, 3 days, 7 days or 21 days after the injection. Control rats were injected with saline and sacrificed either at 8 h or 21 days after the injection. The midbrain region was dissected, RNA was isolated and probed for 5-HTT expression using Northern Blotting. Data were analyzed using Super-Anova followed by posthoc Dunnett's test. While mRNA levels for 5-HTT were unchanged at 8 h after reserpine, a significant decrease was noted at 3 days and 7 days (F = 10; p < 0.0001). 5-HTT mRNA levels returned to control levels by 21 days. In contrast, TPH expression was unaltered at all time points examined. The results of this study provide useful information regarding the role that the 5-HTT may be playing in the homeostatic control of 5-HT neurotransmission at the synapse.

Reserpine does not induce orofacial dyskinesia in spontaneously hypertensive rats

The nigrostriatal dopaminergic system seems to be involved in both reserpine-induced orofacial dyskinesia in normal rats and in the pathogenesis of hypertension in spontaneously hypertensive rats. In the present study, repeated reserpine administration (1.0 mg/kg, s.c., every other day, for 3 days) increased tongue protrusion and vacuous chewing frequencies as well as the duration of facial twitching in Wistar normotensive but not in spontaneously hypertensive rats. These results suggest that genetic hypertension and drug-induced orofacial movements may be inversely modulated by similar mechanisms in the nigrostriatal dopaminergic system.

Cytochemical localization of ouabain-sensitive, K+-dependent p-nitrophenylphosphatase activity in the choroid plexus of normal and reserpinized guinea pigs.

High doses of reserpine induce depletion of biogenic amines. The K-NPPase activity of choroid plexus was determined after one-shot reserpine administration using cerium-based cytochemistry. In normal untreated animals, reaction product was found on the microvilli of the choroidal epithelium but was almost undetectable 3 and 7 days after reserpinization. At 20 days after reserpinization, however, it was detectable. These findings suggested that reserpine decreased the choroidal Na,K-ATPase activity, and that catecholamines might be essential to maintain normal choroidal Na,K-ATPase activity. (J Histochem Cytochem 46: 975-976, 1998)