Effect of triiodothyronine and reserpine on induction and growth of mammary tumors in rats by 3-methylcholanthrene

This study was designed to investigate the effects of exogenous L-triiodothyronine (LT₃) and reserpine administration on the induction and stimulation of 3-methylcholanthrene (3-MC) mammary tumors. Two hundred-fifty-eight 30-day-old virgin 100 gm Sprague Dawley rats were divided into eight groups. Groups I–IV received either reserpine, LT₃, both, or saline 22 days after tumor induction with 3-MC. Groups V–VIII were pretreated with either reserpine, LT₃, or both for 29 days prior to tumor induction, and treatment was continued after tumor induction in all except Group VII. All rats were observed for tumor growth and sacrificed at seven months. Reserpine administration resulted in a protective effect against tumor induction in all groups in which it was used, with the most striking effects observed in the pretreated groups. Early LT₃ stimulation of tumor formation was reversed by simultaneous administration of reserpine. Prolonged administration was unnecessary when both agents were administered prior to 3-methylcholanthrene.     

Long-term potentiation in the dentate gyrus: Effects of noradrenaline depletion in the awake rat

The chronic rat preparation was utilized to study the effects of noradrenaline (NA) depletion on field potentials recorded from the hilus of the fascia dentata. Both single pulses and high-frequency trains were applied to the perforant path (PP). The effects of NA depletion on baseline responses as well as on long-term potentiation (LTP) were examined. Reduced NA levels resulted in an increase in the population spike amplitude and a depression of the population excitatory postsynaptic potential (EPSP). Depleted animals showed significantly higher levels of LTP of the population EPSP, but reduced levels of population spike LTP (measured 13-15 min after tetanization). There were, however, no differences in LTP levels 1 week after the potentiation tests. These results demonstrate that NA levels do not affect that component of LTP which can persist for several weeks.     

Immunohistochemical investigations of the influence of reserpine on the serotonin neuron system in the rat brain

A peroxidase-antiperoxidase immunohistochemical method with serotonin antiserum was employed to investigate the influence of reserpine on serotonin neurons of rats which were sacrificed at various times after injection (10 mg/kg i.p.). The disappearance of serotonin immunoreactivity induced by reserpine was detected only in the perikarya after 15 min, and then rapidly proceeded to the terminals. Between 2 and 4 h, immunoreactivity completely disappeared throughout the brain. The immunoreactivity reappeared in the perikarya after 6 h, and progressed toward the terminals gradually. However, there was an obvious difference in the rate of recovery of immunoreactivity between areas. After 7 days, the immunoreactivity returned to control levels.     

Alpha-methyltyrosine attenuates and reserpine increases methamphetamine-induced neuronal changes

The repeated administration of methamphetamine to rats has been shown to cause a long-lasting depletion of dopamine in various brain regions. In the first study, the effects of pretreatment with alphamethyltyrosine (AMT) or reserpine on the long-lasting methamphetamine-induced dopamine depletion were examined. In the second study, the effects of AMT and reserpine on central dopamine levels were measured in rats previously treated with methamphetamine. Pretreatment with AMT attenuated the long-lasting dopamine depletion induced by methamphetamine, whereas, pretreatment with reserpine increased the depletion. The acute effects of AMT and reserpine on brain dopamine were not altered when administered two weeks after the last methamphetamine injection.     

Effect of Thyroxine,Reserpine and Serotonin on Allyl Alcohol Induced Hepatotoxicity in Rats*

Rats, treated with allyl alcohol (AA), 0.8 %, w/v, 4 ml/kg, orally (group B) and examined 24 hrs later showed an increase in the levels of serum bromsulfphthalein (BSP) (3 ×) and glutamic-pyruvic transaminase (GPT) (5 ×) and periportal hepatic necrosis, as compared with the control (group A). Treatment with thyroxine sodium (T₄), 1.6 mg/kg given orally daily for 6 days (group C) raised the rectal temperature by about 2°. Reserpine, 5 mg/kg intraperitoneally (group D) or serotonin, 5 mg/kg intraperitoneally (group E) lowered the rectal temperature by 1–2° within 1 hr. Groups C, D and E had normal hepatic function and morphology. When group B was treated with T₄ as mentioned above (group F), the increase in BSP and GPT levels (both 8 ×) and the degree of necrosis were more marked. When group B was pretreated with reserpine (group G) or serotonin (group H) 1 hr before AA, the increase in serum BSP (about 1.5 × and 2.5 × respectively) and GPT (about 3.5 × and 4 × respectively) and the degree of necrosis were less pronounced. When group F was also treated with reserpine (group I) the rise in body temperature was reduced from about 2° to about 1° while the serum BSP and GPT levels and the degree of necrosis were brought to near group B levels. When group F was also treated with serotonin (group J) however there was no reduction in body temperature, the serum BSP and GPT levels, or the degree of necrosis. These findings point to a possible direct relationship between body temperature and the hepatotoxic effect of AA.     

Niaprazine, a selective brain catecholamine depletor.

Niaprazine (30–240 mg/kg i.p.) lowered rat brain levels of noradrenaline and dopamine, but did not alter levels of 5-hydroxytryptamine. The maximum depletion (65–70%) was observed 30 min after an injection of 120 mg/kg (i.p.) niaprazine, and total depletion could not be achieved by increasing the dose further. The reduction in levels of catecholamines was short-lasting, and was accompanied by an increase in brain levels of the metabolites DOPAC and MOPEG-SO₄. In contrast to niaprazine, tetrabenazine (20 mg/kg i.p.) lowered the brain levels of 5-hydroxytryptamine as well as the catechol-amines, and increased brain levels of their metabolites, 5-HIAA, DOPAC and MOPEG-SO₄. Reduced brain concentrations of catecholamines were observed 24 hr after an injection of reserpine (1 mg/kg i.p.). Pretreatment with tetrabenazine (20 mg/kg i.p.) prevented the reserpine-induced depletion of brain catecholamines, whereas pretreatment with niaprazine (60 or 180 mg/kg i.p.) did not alter the reserpine-induced depletion. The results indicate that niaprazine depletes brain catecholamines, but differs in its profile of action from reserpine and tetrabenazine.     

Modification of reserpine induced rigidity by dopaminergic and alpha-adrenergic drugs

Previous studies have reported that a variety of drugs are effective in preventing reserpine-induced hypertonus, including dopamine agonists and alpha-adrenergic antagonists. The purpose of this study was to use a quantitative measure of hindlimb muscle tone to evaluate the relative efficacy of various drugs with known pharmacologic actions on dopaminergic and adrenergic receptors. The results show that adrenergic antagonists (yohimbine, thymoxamine, phentolamine, RS 21361) were the most effective in protecting against the effect of reserpine. Along with the dopamine precursor, 1-DOPA, these drugs were not only effective but also they produced no muscle relaxation in non-reserpinized rats. Although dopamine agonists (apomorphine, lisuride, bromocriptine) also protected against reserpine-induced rigidity, these drugs also produced muscle relaxation in non-reserpinized rats. A variety of drugs with alpha adrenergic agonist, beta adrenergic antagonist, dopamine antagonist and antihistamine activity did not alter the reserpine-induced rigidity despite generalized muscle relaxant effects with some of these. The results show that alpha adrenergic antagonists are the most selective agents in preventing reserpine-induced rigidity and suggest that alpha-2 receptors primarily mediate this effect.     

Effects of phencyclidine on synaptosomal dopamine continuously appearing from phenylalanine: Sensitivity to reserpine

In the present study some effects of phencyclidine on synaptosomal (P₂) synthesis and release of labelled dopamine, continuously appearing from [¹⁴C]phenylalanine, were investigated in vitro. Also examined was the sensitivity of such effects of phencyclidine to reserpine, acting either in vitro or in vivo. Synaptosomal (P₂) preparations from rat caudate nuclei were incubated with the drugs added at various concentrations in the presence of [¹⁴C]phenylalanine substrate. The particulates were quickly separated from the medium after incubation and the separated fractions were analyzed for labelled dopamine and the synaptosomal uptake of [¹⁴C]phenylalanine. Of the total labelled dopamine formed, the fraction that was present in the medium was determined and taken as a measure of the spontaneous or basal release and its enhancement by any drug addition. Phencyclidine (3.1–36.4 μM) stimulated both the total (medium plus particulates) formation and the synaptosomal release of labelled dopamine, while reserpine (0.09–1.80 μM) inhibited the formation and enhanced the release. A coaddition of reserpine (0.09–1.80 μM) and phencyclidine to the incubation medium blocked the stimulating effect of the latter drug on the labelled dopamine synthesis; the same experiments revealed furthermore, an inhibitory effect of phencyclidine (0.91–36.4 μM) on the synthesis, an effect that was additive to the inhibition due to reserpine alone. The enhancing effect of phencyclidine on labelled dopamine release was however maintained in the presence of reserpine. Phencyclidine (0.22–36.4 μM) also inhibited the formation of labelled dopamine and enhanced its release when the P₂ fraction was prepared from reserpine-pretreated rats (5.0 and 2.5 mg/kg, i.p., at 24 and 2 hr before the experiment). Reserpine (1.80 μM) itself, added in vitro to the same P₂ preparation, was without any significant effect. The phencyclidine congener Ketamine, with or without reserpine, had little effect either on the synthesis or the release. In none of the incubations did the addition of drugs affect the synaptosomal uptake of labelled phenylalanine.     

The role of calcium in the mechanism of changes in vascular reactivity due to reserpine

Under the influence of reserpine there is a marked decrease in the calcium concentration in segments of the distal aorta and femoral arteries of rabbits, incubated in salt solution. These changes develop parallel with changes in the character of responses of the vascular segments to direct electrical stimulation (weakening of the effects of contraction, followed by relaxation). A decrease in the calcium concentration in the vascular wall is suggested as one cause of the change in vascular reactivity.All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. I. Chazov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp 45–48, July, 1979.     

Evidence for the outward transport of norepinephrine in synaptic vesicles attached to the plasma membrane

In a low-sodium, choline⁺ (Ch⁺) medium, rat heart slices, that were labelled in vivo with [³H]norepinephrine, exhibited a delayed, Ca²⁺-dependent release of radioactivity, these radioactive compounds consisted of both amines and deaminated metabolites. The Ca²⁺-dependent release of radioactivity was largely blocked by cocaine suggesting that the release may represent an outward transport of [³H]amines. Reserpine, which is known to inhibit binding of norepinephrine to synaptic vesicles, stimulated the release of deaminated metabolites and some amines from the slices. Cocaine increased the release of [³H]amines in monoamine oxidase inhibited, reserpinized slices in the control medium. When Ch⁺ -Ca²⁺ and reserpine stimulation were combined, the effects of Ch ⁺ -Ca²⁺ predominated. These effects were blocked by cocaine, which then permitted the response to reserpine to become established. The conclusion derived from the above experiments is that norepinephrine coming from synaptic vesicles brought in close proximity to the plasma membrane by a Ca²⁺-dependent system can be transported outwardly to the extraneuronal space by a cocaine-sensitive mechanism.