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PubMed1980

A comparison of rates of depletion and recovery of noradrenaline stores of peripheral and central noradrenergic neurones after reserpine administration: importance of neuronal activity.

1 The noradrenaline (NA) content of various peripheral sympathetic neuroeffector organs and brain was measured at various times after different doses of reserpine administered to the rat.2 About a 25% reduction in the NA content of the heart was observed 24 h after 0.005 mg/kg reserpine. Two to ten times more reserpine was needed to obtain an approximately similar degree of depletion in the salivary gland and vas deferens; 0.1 mg/kg produced almost complete depletion in the heart and salivary gland, whereas 5 mg/kg was needed to deplete the vas deferens of its NA content.3 The NA content of the brain and superior cervical ganglion was lowered by 20 to 30% in 24 h only when the reserpine dose was raised to 0.1 mg/kg, and 5 to 10 mg/kg was required to obtain over 95% depletion.4 The rates of recovery of cardiac and salivary gland NA stores, after about 80 to 100% depletion by low and high doses of reserpine, were almost identical. About 50% restoration occurred in 7 to 15 days after a single dose of 0.1 mg/kg reserpine.5 The superior cervical ganglion, the NA content of which was fully depleted by 10 mg/kg, showed almost complete recovery in about 7 days.6 Transmural stimulation of the left atrium of the guinea-pig for 30 min (5 Hz for 30 s/min), or exposure of the atrium to reserpine (5 mug/ml) for 30 min, caused modest but statistically insignificant reduction in tissue NA content. However, stimulation in the presence of reserpine 5 mug/ml for 30 min produced about 50% depletion of NA.7In vitro reduction in NA content caused by reserpine plus transmural stimulation, was even more pronounced after treatment of the isolated vas deferens of the rat with tetraethylammonium.8 It is suggested that different rates of depletion following in vivo administration of reserpine are mainly due to variation in neuronal activity of different sympathetic neuroeffector organs.

Animals↗

PubMed1987

Reserpine, vagal adrenergic activity and stress-induced acute gastric mucosal injury in the rat.

1. Stress activates the hypothalamus causing central adrenergic discharge and stimulation of the autonomic sympathetic system. Reserpine produces the same effect and, therefore, its acute gastric mucosal injury is stress-induced. This injury was employed in the gastric diversion rat, a model for determining gastric acid secretion under basal conditions, to examine the relationship of the vagus nerve to the autonomic sympathetic system in the mechanism of stress-induced acute gastric mucosal injury. 2. After 6 h of reserpine (5 mg/kg I.P.), all rats developed oval or round lesions confined to the glandular stomach and of no constant relationship to rugal crests (lesion score 29 +/- 2.7 mm2, mean +/- S.E., n = 10). Microscopically, these lesions were vascular in origin, developing as intramural foci of haemorrhage or necrosis and expanding to communicate with the lumen. Pre-treatment with potent antisecretory doses of the anticholinergic atropine (5 mg/kg I.P.) or the H2-receptor antagonist cimetidine (40 mg/kg I.P.) did not influence this reserpine action (28 +/- 3 mm2 and 27.5 +/- 2.3 mm2, respectively, mean +/- S.E., n = 10). Protection against the reserpine lesions by the alpha-adrenoceptor blocking drugs phenoxybenzamine or phentolamine given in a dose of 10 mg/kg I.P. was significantly (P less than 0.01) more than that afforded by the 5 mg/kg I.P. dose. However, the 15 mg/kg I.P. dose was completely protective against the lesions. Vagotomy had a similar protective effect. Interruption of autonomic sympathetic delivery to the stomach by coeliac ganglionectomy had no influence on the macroscopic or microscopic effects of reserpine on the stomach (30.5 +/- 3.4 mm2, mean +/- S.E., n = 10). 3. The H+ output associated with 6 h of gastric diversion (61 +/- 4.5 mumol, mean +/- S.E.) was significantly (P less than 0.001) depressed by reserpine alone (26 +/- 2 mumol) or with atropine (19 +/- 1.8 mumol) or cimetidine (21 +/- 2 mumol). Protection against the reserpine lesions by phenoxybenzamine or phentolamine was associated with dose-dependent increase of H+ output, which with the 15 mg/kg dose was similar to that of control values (58 +/- 4.1 mumol and 60.3 +/- 2.8 mumol vs. 61 +/- 4.5 mumol). Vagotomy protection was associated with an H+ output significantly (P less than 0.001) lower than that with reserpine alone (14 +/- 1.4 mumol). Coeliac ganglionectomy had no influence on the H+ output associated with reserpine treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1989

Reserpine but not surgical denervation regulates rat renal beta-adrenergic receptors.

The effects of unilateral surgical denervation or reserpine administration on renal beta-adrenergic receptors were examined in rat kidney cortex. The specific binding of [125I]iodocyanopindolol was used to quantitate the beta-adrenoceptors. Denervation had no significant effect on beta-adrenoceptor concentration in denervated compared with contralateral control kidney, 7 days postsurgery. In contrast, reserpine treatment increased beta-adrenoceptor concentration 30% compared with control (P less than 0.05). Tissue norepinephrine levels were depleted to a significant extent with both manipulations. The reserpine effect was investigated further. Reserpine increased both beta 1- and beta 2-adrenergic receptor subtypes to the same extent. The effect of reserpine was primarily on tubular beta-adrenoceptors including those in the proximal tubules; glomerular beta-adrenoceptors were minimally affected by reserpine. Other adrenergic receptor subtypes (alpha 1- and alpha 2-) were also significantly increased by reserpine; however, angiotensin II receptors were not altered, indicating that the reserpine effect was not a general one affecting all membrane receptors. Reserpine treatment increased beta-adrenergic receptor-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by 49% over control in the renal cortex. Denervation had no significant effect on cAMP accumulation. Overall, our results suggest that, in addition to sympathetic nerve terminal norepinephrine, other factors may be involved in the regulation of renal beta-adrenergic receptors.

Animals↗

PubMed1984

Effect of chronic reserpine treatment on the pancreases of neonatal rats.

Chronic reserpine treatment of adult rats results in the accumulation of pancreatic enzymes and reduction of their discharge. These changes are reminiscent of those in cystic fibrosis. Since the majority of cystic fibrosis patients have their pancreatic dysfunction manifested in childhood, we studied chronic reserpine treatment in rat pups. Four-day-old rat pups were given reserpine (50 micrograms/kg intraperitoneally) or vehicle daily until sacrifice. The reserpine group showed significant decreases in body weights at 14 and 21 days of age. Pancreatic weights were also decreased but were of normal weight or increased when normalized against body weights. At 14 and 21 days of age, pancreatic concentrations of amylase, lipase, and trypsinogen showed no difference between reserpine and control pups. At both ages, pancreatic contents of all three enzymes were generally less in the treated pups, but were found to be similar when corrected for body weights. Hydrocortisone treatment of 14-day-old pups caused precocious accumulation of pancreatic enzymes in both reserpine and control groups. Intestinal contents of lipase, trypsin, and amylase were decreased in the reserpine pups at 14 days of age and reached a more significant level at 21 days of age; these data suggest a decrease in the secretion of pancreatic enzymes. Dispersed acini from 14-day-old pups showed a reduced capacity to release amylase as stimulated by carbachol or the octapeptide of cholecystokinin. The results suggested that chronic reserpine treatment of pups in the suckling period did not cause significant disturbance of the developmental accumulation of pancreatic enzymes. A definite inhibition of exocrine secretion was found with reserpine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

PubMed1991

[Modulation of anthracycline resistance by reserpine in P388 leukemia cells].

The activity of reserpine and a possible mechanism by which it reverses the resistance to both doxorubicin and pirarubicin in doxorubicin-resistant P388 leukemia (P388/DOX) cells were examined in vitro. During 48 hr drug-exposure, the sensitivity of doxorubicin and pirarubicin were potentiated markedly when reserpine was present at the concentration of 1 microgram/ml, which is not toxic to P388 leukemia (P388/S) cells. However, reserpine had little effect on the cytotoxicity of doxorubicin and pirarubicin in the sensitive parent cell. Reserpine at 0.5-20 micrograms/ml increased intracellular accumulation of doxorubicin and pirarubicin in the drug-resistant cells. The potentiating action of reserpine was stronger when the cells were preincubated with reserpine within 30 min. Efflux of doxorubicin and pirarubicin was greater in drug-resistant cells compared to sensitive cells. This enhanced efflux of drug resulted in a decrease in the intracellular accumulation of doxorubicin in the drug-resistant cells. When the resistant cells were exposed to 2 micrograms/ml of reserpine, this enhanced efflux was blocked. A similar effect of reserpine on doxorubicin was seen with the efflux pattern of pirarubicin. From the measurements of drug uptake and efflux, it seems that like other multiple drug resistance modifiers, reserpine modulates anthracycline resistance by increasing intracellular accumulation of drug.

Animals↗

PubMed1984

Increase of sensitivity and uptake of vinblastine by reserpine in rat ascites hepatoma.

We investigated the effect of reserpine on the antitumor effect of vinblastine (VBL) with regard to the drug resistance of rat ascites hepatomas. The sensitivity to VBL was in the order of AH13 greater than AH44 greater than AH109A greater than AH66 cells in the in vitro growth-inhibitory test, and AH66 cells were inherently most resistant to VBL. The intracellular accumulation of VBL was lower in resistant cells than in sensitive cells. Reserpine increased the sensitivity to VBL in the order of AH66 greater than AH109A greater than AH44 greater than AH13 cells. The antitumor synergism was also observed in the in vivo experiments using AH44 and AH66. Reserpine enhanced the VBL accumulation more than 2 times in AH66 and AH109A cells, but slightly increased it in AH13 and AH44 cells. These results indicated that the synergistic effect of reserpine was more potent in relatively resistant cell lines to VBL, and the effect was caused by the enhancement of VBL accumulation. On the other hand, the enhanced growth-inhibitory effect and the accumulation of VBL in the presence of reserpine were not influenced by further preincubation with reserpine. Reserpine also did not influence the intracellular level of VBL increased by 2,4-dinitrophenol in a glucose deprived medium. Reserpine decreased the VBL extrusion from AH66 cells more strongly than that from AH44 cells. These results indicated the possibility that reserpine interfered with the VBL efflux process, while it might not influence the VBL influx process.(ABSTRACT TRUNCATED AT 250 WORDS)

2,4-Dinitrophenol↗

PubMed1986

Morphine analgesia without development of tolerance in reserpinized mice.

The relationship between the brain monoaminergic mechanism and morphine tolerance was examined in reserpinized mice. In parallel with the reduction of brain monoamine content, the analgesic effect of morphine was reduced in reserpinized animals. At the peak of the reserpine effect, 24 hr after a single dose of 2.5 mg/kg reserpine, i.p., the analgesic effect of morphine was lowered to about 45% of that in naive animals; and 5 days after reserpine treatment, it recovered to about 60% of the control activity. In these animals, the lowered effect of morphine was maintained at the same range during 6 daily repetitions, and the development of tolerance was suppressed. When daily morphine injection was started from 10 days after reserpine treatment, at the time when the brain level of monoamines was still reduced to 60 to 80% of the control, tolerance developed as rapidly as in control animals. On the other hand, daily treatment with a small dose of reserpine, 0.1 mg/kg, neither affected the brain level of norepinephrine and dopamine nor modified morphine analgesia, but completely blocked the development of tolerance. These results may suggest that suppression of the development of tolerance to morphine analgesia is not attributed to the reduction of brain norepinephrine and dopamine by reserpine. Morphine analgesia without development of tolerance in reserpinized mice may indicate the dissociation of the analgesic effect from tolerance liability.

Animals↗

PubMed1990

Combined reserpine and pituitary irradiation therapy for Cushing's disease patients following unsuccessful transsphenoidal microsurgery.

The effectiveness of treatment with reserpine and pituitary irradiation, and with reserpine alone was evaluated in three female patients with Cushing's disease whose transsphenoidal pituitary microsurgery (TPM) had been unsuccessful. In these patients, endocrinological examination after the surgery demonstrated a recurrence of the disease although the microadenomas had apparently been curetted out from the pituitary in all patients. The first patient therefore received 1.0-2.0 mg/day of reserpine with 60 Gy x-ray irradiation, and there was complete remission within 3 months and the patient remained asymptomatic even when reserpine was reduced to 0.1 mg/day 10 years later. The second case was treated with low dose x-ray (20 Gy) and reserpine (0.5-2.0 mg/day), which were also effective. However, 2 weeks discontinuation of the drug caused urinary 17-hydroxycorticosteroids (17-OHCS) and serum cortisol to increase abnormally again, but these were finally re-normalized by an additional administration of reserpine. The third case was given reserpine alone (1.0-2.0 mg/day). She also had a remission in 3 months and the treatment was continued for one year, requiring no further treatment. These results suggest that additional treatment with reserpine and pituitary irradiation or with reserpine alone after unsuccessful TPM may be an effective alternative for patients with Cushing's disease.

17-Hydroxycorticosteroids↗

PubMed1976

In vitro alteration of the subcellular distribution of 3H-reserpine in the rat forebrain by delta 9-tetrahydrocannabinol.

delta 9-Tetrahydrocannabinol (delta 9-THC) has been reported to attenuate both reserpine-induced serotonin depletion and reserpine-induced hypothermia. We have observed that delta 9-THC preincubation led to a dose-responsive increase in the amount of 3H-reserpine bound to a crude mitochondrial fraction of rat forebrain. The experiments reported here further characterize this phenomenon. Preincubation with delta 9-THC produced a shift in the localization of 3H-reserpine from the incubation medium and the microsomal supernatant (decrease of 66%) to the crude mitochondrial (CM) pellet (increase of 154%). The CM pellet was subfractionated both by differential centrifugation after osmotic shock and by layering on a five-step discontinuous sucrose gradient and centrifuging at 80,000 x g. Osmotic shock with 0.032 M sucrose and centrifugation revealed that the delta 9-THC-induced increase in 3H-reserpine was contained in both the synaptic vesicle fraction (247%) and the fraction containing myelin, ruptured synaptosomes and mitochondria (324%). Separating the CM fraction into five component parts showed that delta 9-THC increased the 3H-reserpine bound by about 275% in the three fractions containing myelin, membrane fragments or mitochondria. Even more dramatic increases (greater than 1000%) were observed in the two fractions containing cholinergic and non-cholinergic nerve endings. In addition, we have determined that many other drugs which are believed to have membrane mediated mechanisms have no effect on the amount of 3H-reserpine bound to the crude mitochondrial fraction. Although other possibilities exist, these data support the hypothesis that delta 9-THC retards the action of reserpine by altering the normal distribution of reserpine in various membrane components of the rat brain.

Animals↗

PubMed2000

Effect of dopaminergic drugs on the reserpine-induced lowering of hippocampal theta wave frequency in rats.

The effects of dopaminergic drugs on the lowering of hippocampal theta wave frequency induced by reserpine 1 mg/kg s.c. were examined. Sibutramine (monoamine reuptake inhibitor) 10 mg/kg p.o., methamphetamine (monoamine releaser) 1 mg/kg, quinpirole (dopamine D2 receptor agonist) 10 mg/kg i.p., and SKF 38393 (dopamine D1 receptor agonist) 10 mg/kg i.p. each antagonized the reserpine-induced lowering of hippocampal theta wave frequency in rats. Moreover, the combined administration of SKF 38393 1 mg/kg i.p. and quinpirole 1 mg/kg i.p. synergistically antagonized a reserpine-induced lowering of this frequency. Dosulepin, amitriptyline, and desipramine, which are weak inhibitors of dopamine reuptake, each had little effect on the reserpine-induced lowering of theta wave frequency at a dose of 40 mg/kg p.o. Furthermore, atropine (muscarinic anticholinergic drug) 20 mg/kg p.o. decreased theta wave power in the low-frequency range following a shift to the lower range by reserpine. A positive correlation was observed for each of the above drugs between a reversal of reserpine-induced lowering of theta wave frequency and a reversal of impairment of reserpine-induced conditioned avoidance responses (ACAR) in rats. These results suggest that the reserpine-induced lowering of hippocampal theta wave frequency plays a role in the impairment of reserpine-induced ACAR, and that dopamine D1 and D2 receptors play important roles in antagonizing this lowering of frequency.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1990

Reserpine up-regulation of rat renal cortical beta adrenergic receptors is independent of its effect on the sympathetic nervous system.

Experiments were performed to evaluate the mechanism underlying our recent observation that reserpine but not surgical denervation up-regulates rat renal cortical beta adrenergic receptors. The specific binding of [125I]iodocyanopindolol was used to quantitate the beta adrenoceptors. Chronic high-dose guanethidine, which decreased renal tissue and circulating catecholamines to the same extent as reserpine, failed to up-regulate renal beta adrenoceptors, which indicates that the effect of reserpine was not due to changes in the ambient catecholamine concentration. Isoproterenol-stimulated renin secretion, a measure of postsynaptic receptor function, was increased by reserpine but not denervation, which indicates that the failure to observe beta adrenoceptor up-regulation by radioligand binding studies after denervation was not an anomaly caused by loss of presynaptic receptors masking postsynaptic supersensitivity. Reserpine was effective even in denervated kidneys. Up-regulation of renal beta adrenoceptors with reserpine occurred even after destruction of peripheral sympathetic nervous system by a combination of adrenal demedullation and high-dose guanethidine administration. A lower daily dose of reserpine (0.3 mg/kg instead of 0.5 mg/kg), which caused no weight loss, was effective in producing beta adrenoceptor up-regulation. Antagonism of reserpine depletion of nerve terminal norepinephrine by tranylcypromine, a monoamine oxidase inhibitor, did not nullify renal beta adrenoceptor up-regulation. Overall, our results indicate that reserpine up-regulation of renal beta adrenergic receptors is independent of the sympathetic nervous system and possibly is a direct effect.

Adrenergic beta-Antagonists↗

PubMed1991

Effect of reserpine on histamine metabolism in the mouse brain.

The effect of reserpine on brain histamine (HA) metabolism in vivo was examined in mice. The level of tele-methylhistamine, a major metabolite of HA, was decreased dose-dependently by reserpine (1-5 mg/kg s.c.), whereas the HA level was unaffected. This effect was observed in all brain regions examined. The accumulation of tele-methylhistamine induced by pargyline (65 mg/kg i.p.), an inhibitor of monoamine oxidase, was inhibited to 19% of the control value 24 hr after the treatment with reserpine (5 mg/kg s.c.). However, the HA decrease induced by (S)-alpha-fluoromethylhistidine (50 mg/kg i.p.) a specific inhibitor of histidine decarboxylase, was not significantly affected by pretreatment with reserpine (5 mg/kg s.c.) 1 or 24 hr before. The HA increase induced by metoprine (10 mg/kg i.p.), an inhibitor of histamine-N-methyltransferase, or by L-histidine (0.5-1.5 g/kg i.p.) was inhibited markedly by pretreatment with reserpine. This effect was more marked when reserpine was administered 1 hr than 24 hr before. In addition, the L-histidine-induced increase in HA level was enhanced markedly by the simultaneous administration of metoprine in the control mice but not in the mice treated with reserpine 1 hr before L-histidine injection. From these results the following are suggested. 1) There may be both of reserpine-resistant and reserpine-sensitive HA pools in histaminergic nerve endings. 2) Most of the neuronal HA in the brain may be located in the former pool. 3) However, the capacity of the former pool may be limited and thus most of the increased HA by L-histidine and metoprine may be transferred into the latter pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Reserpine-induced postjunctional supersensitivity in rat vas deferens and caudal artery without changes in alpha adrenergic receptors.

Caudal artery and vas deferens from rats treated chronically with reserpine (1 mg/kg/day i.p.) were used to study drug-induced postjunctional supersensitivity in smooth muscle. There was no change in contractile sensitivity of the rat vas deferens after 1 day of reserpine treatment; however, there were similar increases in sensitivity 4 and 7 days after reserpine treatment. The potencies of phenylephrine, methacholine and potassium chloride in causing contraction of the vas deferens were significantly increased by 4.9-, 19.5- and 1.23-fold, respectively, after 7 days of chronic treatment. This treatment also increased the potencies of phenylephrine, serotonin and potassium chloride in causing contraction of rat caudal artery by 1.8-, 1.7- and 1.23-fold, respectively; however, the potency of clonidine was unchanged after 7 days of reserpine treatment. There was no change in sensitivity to phenylephrine 1 day after reserpine treatment but sensitivity was significantly increased after 4 days. There was no significant change in maximum contractile response in either tissue to any of these agents after chronic reserpine treatment. Scatchard analysis of saturation isotherms of specific [125I]BE 2254 binding to membrane fractions from rat vas deferens and caudal artery showed no change in the density or affinity of alpha-1 adrenergic receptors after 1, 4 or 7 days of chronic reserpine treatment. In addition, no change was observed in specific [3H]rauwolscine binding to either tissue after 7 days of chronic reserpine treatment, suggesting no change in alpha-2 adrenergic receptors. These data indicate that changes in alpha adrenergic receptors are not involved in postjunctional supersensitivity of smooth muscle caused by chronic reserpine treatment.

Animals↗

PubMed1984

Identification and characterization of the catecholamine transporter in bovine chromaffin granules using [3H]reserpine.

Characterization of the catecholamine transporter in chromaffin granule membranes has been hampered by the lack of a radioligand with high specific activity which binds selectively to the carrier with high affinity. We report here the identification of a high affinity binding site for [3H]reserpine on chromaffin granule membranes isolated from bovine adrenal gland which has the characteristics expected of the catecholamine transporter. [3H]Reserpine bound predominately to a high affinity site with a Kd for [3H]reserpine of 9 nM and a binding site density of 7.8 pmol/mg of protein. Comparison of the characteristics of the high affinity reserpine binding site to the characteristics of catecholamine transport indicated that (a) the Ki and rank order of potency for inhibition of [3H]reserpine binding by various biogenic amines was similar to their Ki for inhibition of catecholamine transport (b) both the inhibition of (-)-[3H]norepinephrine transport and inhibition of [3H]reserpine binding showed similar stereo-specificity, and (c) Kd for binding of reserpine to chromaffin granule membranes was similar to the Ki for reserpine inhibition of catecholamine transport. These results demonstrate that the high affinity binding site for [3H]reserpine on chromaffin granule membranes is associated with the catecholamine transporter.

Adrenal Medulla↗

PubMed1982

Effect of reserpine pretreatment on guinea pig ventricular performance and responsiveness to inotropic agents.

Demonstration of reserpine-induced inotropic supersensitivity depends on such variables as the dose and time course of reserpine pretreatment, the species, the agonist being tested, the experimental preparation, the frequency of stimulation and possible cardiotoxic effects of reserpine. We therefore carried out a systematic investigation of the effects of reserpine pretreatment on the performance and responsiveness of working guinea-p]ig hearts to a variety of inotropic agents at different frequencies of stimulation. Preliminary studies of three pretreatment schedules showed that one dose of reserpine (2.5 mg/kg/day for 2 days) increased left ventricular performance by vertically displacing the pressure-work curve (37 degrees C,. 250 beats/min). This dose of reserpine had no effect on coronary vascular resistance. The increase in performance was interrelated with an inotropic supersensitivity to calcium, characterized by an increase in +dP/dt, left ventricular pulse pressure and stroke work at calcium concentrations ranging from 1.0 to 4.0 mM, without a change in estimated pD2 values for calcium. The supersensitivity to calcium was frequency-dependent; it was present at 250 beats/min, but absent at frequencies of 275 beats/min or higher. Reserpine pretreatment increased the inotropic potency (pD2) of dl-isoproterenol (beta), but had no effect on the potencies of histamine (H2), phenylephrine (alpha) or pyridylethylamine (H1). The results show that reserpine pretreatment (2.5 mg/kg/day, 2 days) selectively increased the inotropic responsiveness of working guinea-pig hearts to calcium and to isoproterenol. They further suggest that the mechanisms for these two effects of reserpine are probably different.

Animals↗

PubMed1982

Possible mechanisms involved in the hyperthermic effect caused by reserpine after pretreatment with amphetamine or tranylcypromine in conscious rat.

Reserpine injected intravenously induced a hyperthermic response in rats pretreated one hour before with amphetamine or tranylcypromine. Pretreatment of rats with alpha-methyl-p-tyrosine (alpha-MT) before the interaction of tranylcypromine-reserpine or amphetamine-reserpine, significantly blocked the potentiation of the increase in temperature that was seen after reserpine. Pretreatment with p-chloro-phenyl-alanine (PCPA) partially abolished the potentiation of the increase in temperature that was seen after reserpine. The dopamine receptor antagonists prevented the hyperthermia induced by the interaction of tranylcypromine-reserpine. However, they only partially inhibited the rise of body temperature induced by reserpine in rats pretreated with amphetamine. Methysergide, a serotoninergic receptor blocker, only reduced the hyperthermic effect in both instances. In conclusion, in the rat potentiation of the increase in temperature induced by tranylcypromine before reserpine would appear to involve a main dopaminergic component and a lesser but significant noradrenergic and serotoninergic component. However, in hyperthermia induced by the combination of amphetamine plus reserpine it is unknown which of these amines plays a predominant role in the development of hyperthermia.

Amphetamine↗

PubMedDate not supplied

The effect of drugs interfering with biogenic amines metabolism on gastric secretion and reserpine-ulcers development in rats.

The effect of drugs interfering with endogenous catecholamines metabolism on gastric secretion and gastric ulcers development 4 hr following reserpine administration was investigated in rats with chronic gastric fistulas. Drugs inhibiting catecholamine synthesis: alpha-methyl-p-tyrosine (alpha-MT) and sodium diethyldithiocarbamate (DDC) decreased substantially the reserpine-induced gastric acid and pepsin secretion, but only alpha-MT diminished the development of gastric ulcers. Pretreatment with nialamide (NLD) elicited in reserpinized rats a marked inhibition both of gastric secretion and of gastric ulcers development. Dopamine (DA), noradrenaline (NA) and adrenaline (A) decreased the secretion of hydrochloric acid but did not change the intensity of gastric ulcers caused by reserpine. Desipramine strongly inhibited reserpine-induced gastric acid secretion. Reserpine depleted DA, NA and 5-HT stores in the brain and decreased DA and 5-HT levels in the wall of the stomach in which the NA levels were increased. The changes in biogenic amines content induced by drugs in reserpinized rats did not correlate with their influence on gastric secretion and on the development of mucosal ulcers. The inhibitory effect of all of the drugs examined on gastric acid and pepsin secretion in reserpinized rats was accompanied by the inhibition of gastric ulcers formation following NLD and alpha-MT administration only, indicating that ulcer generation following reserpine depends more on changes in mucosal barrier resistance than on gastric acid secretion.

Animals↗

PubMed1994

Electrophysiological effects of SKF 38393 in rats with reserpine treatment and 6-hydroxydopamine-induced nigrostriatal lesions reveal two types of plasticity in D1 dopamine receptor modulation of basal ganglia output.

To examine the role of D1 dopamine receptors in modulating basal ganglia output and how this role may be altered by changes in dopaminergic transmission, the effects of a D1 dopamine agonist on firing rates of substantia nigra pars reticulata (SNpr) neurons were determined in reserpine-treated rats and compared with effects observed in nigrostriatal-lesioned and normal rats. It was confirmed that systemic administration of the D1 dopamine agonist SKF 38393 (10 mg/kg i.v.) induces a small (averaging 20% above base line) increase in firing rates of SNpr neurons in normal rats and significantly inhibits SNpr single unit activity in rats studied 6 to 26 weeks after 6-hydroxydopamine (6-OHDA)-induced substantia nigra dopamine cell lesion. In contrast to results obtained after 6-OHDA lesions, SKF 38393 administration consistently and significantly increased the firing rates of SNpr neurons in rats treated for 6 days with reserpine (1 mg/kg/day s.c.); increases averaged 88% above base line. Five days after the 6-day reserpine treatment was discontinued, administration of SKF 38393 still induced a pronounced increase in SNpr activity. These increases were reversed by the administration of the D1 dopamine antagonist SCH 23390. SKF 38393 also significantly increased the firing rates of a subpopulation of SNpr neurons in rats treated with only a single dose of reserpine (10 mg/kg s.c. 4-7 hr). The difference between responses in reserpine and 6-OHDA-treated rats was not due to the shorter time course of the reserpine treatments, as SKF 38393 did not consistently affect the activity of SNpr neurons 7 days after 6-OHDA nigral dopamine cell lesion. When the subchronic reserpine treatment was administered to rats lesioned previously with 6-OHDA, D1 dopamine agonist-mediated inhibition of SNpr neuronal activity was obtained. The results show that SNpr responses to D1 dopamine agonist administration after reserpine treatment are enhanced ("supersensitive") relative to normal, whereas SNpr responses to D1 dopamine agonists in animals with 6-OHDA-induced dopamine cell degeneration are opposite to those observed in normal and in reserpinized animals. Current models of basal ganglia function predict that D1 dopamine agonists should reduce activity in the SNpr, because D1 dopamine receptors on striatonigral neurons are thought to stimulate striatonigral firing rates and to enhance the release of tau-aminobutyric acid in the SNpr. The present results call for modification of these concepts.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗