Acute Reserpine Administration Research Articles

The effects of acute reserpine administration on the sensitivity of the isolated pacemaker from rat heart to isoprenaline and noradrenaline.

The effects of reserpine on the sensitivity of the isolated pacemaker from rat heart to the chronotropic effect of isoprenaline and noradrenaline were studied. A single large dose of reserpine (2.5 mg kg-1) administered to rats 24 h before killing induces supersensitivity of the isolated pacemaker to isoprenaline, leaving unaltered the responsiveness of the pacemaker to noradrenaline. Reserpine at the dose of 1.0 mg kg-1 did not alter the sensitivity of the pacemaker to the catecholamines. Only the larger dose of reserpine raised the corticosterone plasma level. It is possible that a corticosterone-mediated inhibition of the extraneuronal uptake process is responsible for the supersensitivity to isoprenaline. Large doses of reserpine should not be used in experiments aimed to study cardiac sensitivity to isoprenaline or extraneuronal uptake and metabolism of the catecholamine.

Effects of age on reserpine-induced orofacial dyskinesia and possible protection of diphenyl diselenide

Acute reserpine administration produces persistent oral dyskinesia in rats, an alleged animal model of tardive dyskinesia. The pathophysiology of the syndrome remains unclear, but experimental evidence suggests that neurodegeneration in the basal ganglia caused by oxidative stress plays a pivotal role in TD development. In this paper, the authors examined whether diphenyl diselenide, an organochalcogen with antioxidant properties, changes the behavioral and neurochemical effect of acute reserpine administration in old rats. The basal vacuous chewing movements (VCMs) and facial twitching (FT) duration was higher in old rats (15 months of age), when compared with adult rats (3 months of age; 0.01). Basal thiobarbituric acid-reactive species (TBARS) levels were increased only in the cortex of old rats, when compared to adult animals ( p < .05). Reserpine injection (1 mg/kg, s.c. for 3 days every other day) caused a significant increase on the tongue protusion (TP) frequency ( p < .01) and facial twitching duration ( p < .01) in old rats. Diphenyl diselenide (10 mg/kg, i.p. for 4 days, starting the day before reserpine) reversed only reserpine-induced TP increase ( p < .01). Reserpine caused a significant increase in striatal TBARS levels ( p < .01) and diselenide reversed ( p < .01) the effect of reserpine on TBARS levels in the striatum. In subcortical parts, isolated reserpine or diselenide administration significantly increased ( p < .01) the levels of TBARS, while simultaneous treatment with reserpine and diselenide reverted this effect ( p < .01). The results of the present study confirmed the effects of age on orofacial dyskinesia. Diphenyl diselenide, an organochalcogen with antioxidant properties, showed modest effects on reserpine-induced orofacial dyskinesia. However, additional studies are still necessary to establish whether this compound can be considered an effective antioxidant in other models of neurotoxicity.

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.

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.

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.

Acute reserpine administration elicits long-term spontaneous oral dyskinesia

Chronic reserpine administration produces persistent oral dyskinesia accompanied by severe dopamine depletion in the caudate-putamen. The present study examined whether these behavioral and neurochemical effects would persist following acute reserpine administration. Acute administration of reserpine (1 mg/kg, s.c.) produced spontaneous oral dyskinesia that persisted above control levels for at least 84 days. Reserpine also produced a 74% depletion of dopamine in the caudate-putamen relative to vehicle treatment at 3 days post-injection, but did not significantly alter dopamine in the caudate-putamen at 84 days post-injection. The finding that reserpine-induced oral dyskinesia persisted despite repletion of dopamine in the caudate-putamen suggests that the persistent neuropathological change underlying this behavior occurs in a neural pathway other than the dopaminergic nigrostriatal pathway.

A Transgenic Mouse Model to Study Transsynaptic Regulation of Tyrosine Hydroxylase Gene Expression

Previous studies demonstrated that 9 kb of the rat tyrosine hydroxylase (TH) 5' flanking sequence directed appropriate spatiotemporal expression of a lacZ reporter gene to catecholaminergic cells in the CNS of transgenic mice. In the present study, specificity of transgene expression was further extended to demonstrate cell type-specific functional regulation of lacZ expression using manipulations known to alter endogenous TH expression. Alterations in lacZ reporter expression should parallel changes in endogenous TH levels if the DNA elements mediating these functional changes of TH expression in vivo reside within the 9 kb of the TH promoter region. Naris closure induced an activity-dependent decrease of TH expression in dopaminergic periglomerular cells in the olfactory bulb that was paralleled by down-regulation of lacZ expression in the transgenic mice. Densitometry and image analysis were used to quantify lacZ expression following acute reserpine administration (5 mg/kg s.c.), which up-regulates endogenous TH. At 48 h postinjection, analysis of OD values indicated a significant increase of X-gal staining in the locus coeruleus and ventral tegmental area but not in the substantia nigra or olfactory bulb of reserpine-treated transgenic animals. These data showed that the 9-kb sequence also mediates cell type-specific transsynaptic regulation of reporter gene expression. Analysis of this transgenic animal offers a useful model system to study in vivo regulation of TH gene expression.

The effect of acute reserpine administration on the uncoupling protein mRNA levels in the mouse brown adipose tissue.

The effect of acute reserpine administration on the uncoupling protein mRNA levels in the mouse brown adipose tissue.

Vacuous jaw movements in rats induced by acute reserpine administration: Interactions with different doses of apomorphine

Two experiments were conducted to study the vacuous jaw movements induced in rats by acute administration of the monoamine-depleting agent reserpine. In the first experiment, different doses of reserpine (1.25, 2.5, and 5.0 mg/kg) were assessed for their ability to induce vacuous jaw movements. Acute administration of reserpine induced a dose-related increase in vacuous jaw movements, with the two highest doses being significantly different from the vehicle control. In the second experiment, interactions between 5.0 mg/kg reserpine and the dopamine agonist apomorphine were investigated. Coadministration of reserpine with the lowest dose of apomorphine (0.1 mg/kg) significantly increased vacuous jaw movements relative to reserpine alone. The two higher doses of apomorphine (0.5 and 1.0 mg/kg) significantly decreased vacuous jaw movements in reserpine-treated rats. These results demonstrate that vacuous jaw movements are induced by acute reserpine treatment in a dose-related manner. In addition, the interactions with apomorphine suggest that vacuous jaw movements are stimulated by decreases in dopamine release produced by low doses of apomorphine that are thought to have mainly presynaptic actions, but that these movements are decreased by higher doses of apomorphine that are known to act postsynaptically.

Preferential expression of superoxide dismutase gene in the neuromelanin-pigmented neurons of the substantia Nigra: Implications for parkinson's disease

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.

Differential effect of acute reserpine administration on D-1 and D-2 dopaminergic receptor density and function in rat striatum

In the present study we investigated the effects of a single injection of reserpine on dopamine receptor function in rat striatum. The measurement of adenylate cyclase activity indicated that cAMP formation induced by the selective D-1 agonist SKF 82526 was greatly increased 2 and 20 h after reserpine; in contrast, the selective D-2 agonist bromocriptine inhibited by the same extent and with the same potency AC in controls and reserpinized striata. In addition, the density of both D-1 and D-2 receptors, as measured in binding studies with the selective D-1 antagonist [ 3H]SCH 23390 and with [ 3H]spiroperidol respectively, was not affected by the treatment. These results suggest that acute reserpine administration induces a selective up-regulation of the transduction mechanisms associated with D-1 receptors, without changing the functional activity of D-2 receptors.

A study on regional brain calcium concentrations following acute and prolonged administration of ethanol in rats

Regional brain calcium concentrations were assessed after acute and chronic ethanol administration. Prolonged exposure to ethanol was accomplished by a 10-day inhalation procedure. Acute administration of ethanol in doses of 1.0, 2.0, and 3.0 g/kg failed to alter calcium content in the cerebellum, cortex, hypothalamus, midbrain, and pons-medulla 30 min after injection. However, ethanol at 4.0 g/kg reduced brain content in the hypothalamus, midbrain, and pons-medulla. When a 90-min interval between ethanol administration (2.0 g/kg) and sacrifice was used, no change was found in the calcium concentration of the five regions examined. During the induction of physical dependence on ethanol, no alteration in the brain calcium content was observed when compared with controls. In the withdrawal phase, which followed 10 days of ethanol inhalation, regional brain calcium concentrations were similar to control values. These animals were monitored up to 7 days postexposure. In experiments which involved acute administration of reserpine (5 or 10 mg/kg), it was shown that the 10 mg/kg dose decreased calcium content only in the hypothalamus by 19.6%. Based on the data derived from this investigation it appears that calcium ions may have a limited role, if any, in the central actions of ethanol when steady-state calcium ion concentrations are considered.

Possible Involvement of a Central Noradrenergic System in Automutilation Induced by Clonidine in Mice

Automutilation induced by a single large dose of clonidine was potentiated by pretreatment with methamphetamine, caffeine and theophylline, while it was inhibited by acute administration of reserpine, α-methyl-p-tyrosine, phenoxybenzamine, phentolamine and chlorpromazine. l-Dopa, 5-hydroxytryptophan and p-chlorophenylalanine had no effect on this abnormal behavior. Biochemical studies on brain monoamines revealed that noradrenaline was markedly increased and dopamine slightly so, but 5-hydroxytryptamine was never changed by clonidine. These results suggest that a central noradrenergic system may be involved in automutilation induced by clonidine in mice.

Unmasking of sympathetic vasoconstruction of the coronary vessels after acute administration of reserpine to dogs.

Acute intravenous administration of reserpine or pretreatment of dogs with Segontin selectively abolished coronary vasodilation and unmasked a constrictor response to stimulation of the cardiac sympathetics. In view of earlier findings of separate coronary vasomotor and cardiostimulatory sympathetic innervation, the results are interpreted to indicate the existence of reserpine-resistant short (vasomotor) and reserpine-sensitive long (cardiostimulatory) sympathetic postganglionic neurons.

Further evidence for 'active' reflex vasodilation.

Further experimental evidence has been presented which strengthens the hypothesis of active reflex dilatation. The administration of a ganglionic blocking agent in a dose sufficient to block completely adrenergic tone failed to lower the perfusion pressure in the isolated extremity to the same level as was reached during the nadir of reflex dilatation. Thus, it is reaffirmed that simple withdrawal of adrenergic vascular tone (passive reflex dilatation) cannot entirely account for the total magnitude of reflex dilatation. Although chronic reserpine pretreatment eliminated both reflex constriction and dilatation, acute reserpine administration reduced reflex dilatation at a time when reflex constriction and perfusion pressure were little affected. On the other hand, the administration of the substituted phenothiazine, methotrimeprazine, eliminated adrenergic tone but had little effect on reflex dilatation. The latter two types of experiment provide further important dissociations between reflex dilatation and inhibition of existing adrenergic activity. Administration of cocaine by several different routes reduced reflex dilatation, but the reduction in reflex dilatation does not appear to be due to inhibition of reuptake of adrenergic amine. Neither does blockade of active reflex dilatation by the antihistamine, tripelennamine, appear to be related to its possible ability to block reuptake of adrenergic amine. Classic autoregulatory stimuli fail to elicit a response analogous to active reflex vasodilatation, and antihistamines fail to alter autoregulatory readjustments while reducing very effectively active reflex vasodilatation.

Modification of some actions of guanethidine by the acute administration of reserpine.

The pressor action of guanethidine (4 mg/kg) is enhanced by previous administration of reserpine (2 mg/kg), when the time elapsing between the injections of the two drugs is varied between 2 min and 8 hr. This enhancement was observed in the dog (anaesthetized, or spinal or nialamide-pretreated animals) and in the cat. The pressor effects of adrenaline and noradrenaline were not modified by reserpine. Guanethidine caused the nictitating membrane of the dog and the cat, as well as isolated cat spleen strips, to contract and the contractions were enhanced by reserpine; however, the contractions of the nictitating membrane induced by electrical stimulation of the postganglionic sympathetic nerve were not changed by reserpine. Similarly, the pressor effect caused by electrical stimulation of the central end of the vagus nerve was not enhanced. Several mechanisms are discussed in order to explain the observed potentiation; the results are in good agreement with the hypothesis of the existence of different noradrenaline pools.

Interaction between the effects of tremorine and harmine and of other drugs in chicks

Responses to tremorine and harmine were recorded in conscious chicks. The tremor response to tremorine was depressed by atropine, hyoscine, propantheline, orphenadrine, benzhexol, chlorpromazine, morphine, hemicholinium, α-methyldopa, 5-hydroxytryptamine and 5-hydroxytryptophan, and was potentiated by amphetamine, dopamine, dopa and physostigmine. Small doses of deaner potentiated and large doses depressed the response. Acute administration of reserpine or tetrabenazine depressed whereas chronic administration potentiated the response. Chlorpromazine, 5-hydroxytryptamine, 5-hydroxytryptophan, amphetamine, dopamine dopa, reserpine and tetrabenazine affected the tremor response to harmine in a similar way to that of tremorine.