Biomedical subjects

C M Contreras

Publications and source records attributed to C M Contreras.

At least 19 recordsLinked to original sources

PubMed2003

A review of clinical and experimental observations about antidepressant actions and side effects produced by Hypericum perforatum extracts.

Hypericum perforatum is an herbaceous perennial plant, also known as "St. John's wort", used popularly as a natural antidepressant. Although some clinical and experimental studies suggest it has some properties similar to conventional antidepressants, the proposed mechanism of action seems to be multiple: a non-selective blockade of the reuptake of serotonin, noradrenaline and dopamine; an increase in density of serotonergic and dopaminergic receptors and an increased affinity for GABAergic receptors; moreover, the inhibition of monoaminoxidase enzyme activity has been involved. In any case, the increase of monoamine concentrations in the synaptic cleft resembles several actions exerted by clinically effective antidepressants. In the present article, we review some of the controversial evidence derived from clinical and experimental studies suggesting that H. perforatum exerts antidepressant-like actions, and we also review some of its side effects, such as nausea, rash, fatigue, restlessness, photosensitivity, acute neuropathy, and even episodes of mania and serotonergic syndrome when administered simultaneously with other antidepressant drugs. All of the foregoing suggests that H. perforatum extracts appear to exert potentially significant pharmacological activity involving several neurotransmission systems supposed to be involved in the pathophysiology of depression. However, little information regarding the safety of H. perforatum is available, including potential herb-drug interactions. There is a need for additional research on the pharmacological and biochemical activity of H. perforatum, as well as its side-effects and its several bioactive constituents to further elucidate the mechanisms of antidepressant actions.

Antidepressive Agents↗

PubMed2001

Diazepam increases the number of punished responses in a conflict-operant paradigm during late proestrus and estrus in the Wistar rat.

Both anxiety-like behavior and the response to anxiolytic drugs vary according to the estrus cycle in the rat. Consequently, anxiety-like behavior and the sensitivity to anxiolytic drugs may be related to hormone level fluctuations occurring during the estrus cycle. In male rats tested in a conflict-operant paradigm, anxiolytic drugs increase immediate punished responding. However, it is unknown whether estrus phases impinge on the immediate punished responses in a conflict-operant paradigm. Therefore, in this study female rats were trained in a conflict-operant paradigm; after training all animals received vehicle or diazepam. Then the number of immediate punished reinforcers was evaluated during the estrus cycle. Results showed that vehicle-treated rats evaluated during late proestrus and estrus obtained a higher (p < 0.05) number of immediate punished reinforcers than rats evaluated during metestrus and diestrus. A low dose of diazepam (1.3 mg/kg; i.p) significantly increased (p < 0.05) the immediate punished responses only in late proestrus and estrus. The highest dose of diazepam tested (2.0 mg/kg; i.p.) significantly increased (p < 0.05) the immediate punished reinforcement in any estrus phase. These results suggest that a lower level of anxiety-like and an increased sensitivity to an anxiolytic drug occurred only in late proestrus and estrus in rats tested in a conflict-operant paradigm.

Animals↗

PubMed2001

The lowest effective dose of fluoxetine in the forced swim test significantly affects the firing rate of lateral septal nucleus neurones in the rat.

The administration of a relatively high dose of antidepressant drugs produces an increased neuronal firing rate of the lateral septal nucleus (LSN) in the rat and a decreased immobility in rats forced to swim. However, it is unknown whether a minimally effective low-dose 21-day treatment with the selective serotonin reuptake inhibitor, fluoxetine, while reducing immobility in the forced swim test, also increases the neuronal firing rate of the LSN in Wistar rats. The total time of immobility decreased with a daily injection of 0.5, 1.0 or 2.0 mg/kg of fluoxetine (p < 0.001), and the lowest dose increasing the latency to the first immobility period (p < 0.0001) was 1.0 mg/kg. Therefore, the action of the 21-day fluoxetine treatment (1.0 mg/kg) on the firing rate of LSN neurones was tested in another group of rats. A total amount of 78 single-unit extracellular recordings was taken from the LSN of eight control rats (n = 40) and eight fluoxetine treated rats (n = 38). The LSN firing rate in the fluoxetine group was double (18.3 +/- 2.5 spikes per 10 s, p < 0.05) that in the control group (7.0 +/- 0.9 spikes per 10 s), and the first order interval of firing proved to be significantly lower in the fluoxetine group compared to the control group (384.3 +/- 22.3 and 639.7 +/- 27.5 ms, respectively; p < 0.05). In conclusion, the increased neuronal tiring rate of the LSN in the animals treated with a low dose of fluoxetine may be associated with an increased motivation to escape from the stressful situation that the forced swim represents.

Animals↗

PubMed2000

Antidepressant-like effects of pregnancy and progesterone in Wistar rats as measured in the differential reinforcement of the low-rate 72 s task.

RATIONALE: In rats, several behavioral changes occurring during pregnancy could be due to the presence of progesterone; some of them may be analyzed in the differential reinforcement of the low-rate 72 s task (DRL-72 s), which is designed for testing the antidepressant profile of drugs. OBJECTIVES: The aim of the present study was to analyze the behavior of pregnant rats or ovariectomized rats receiving exogenous progesterone in the DRL-72 s task. HYPOTHESIS: During pregnancy, rats will obtain a high number of reinforcers in the DRL-72 s task. METHODS: Pregnant rats or rats after delivery were tested in the DRL-72 s task at the 3rd, 7th, 14th, 17th, and 20th days. Control rats previously trained in the DRL-72 s task were ovariectomized; after recuperation, they received saline (0.9%, i.p.), clomipramine (1.25 mg/kg, i.p.), or desipramine (2.14 mg/kg, i.p.) for 28 days, and they were tested in the DRL-72 s task. In a second series of experiments, ovariectomized rats received vehicle or progesterone (0.5, 1.0, 2.0, 4.0 mg/kg, s.c.), and they were submitted to the DRL-72 s task. Locomotion was evaluated in the open field test. RESULTS: Pregnant rats tested at the 14th and 17th day and ovariectomized rats receiving progesterone or two tricyclic antidepressants obtained a higher number of reinforcers and a cohesive rightward shift in inter-response time distributions than those rats evaluated after delivery in the DRL-72 s task. A lower locomotion was observed only at the end of pregnancy. CONCLUSIONS: Antidepressant-like effects of pregnancy and progesterone were found in Wistar rats as measured in the DRL-72 s task.

Animals↗

PubMed2000

Lateral septal neuronal firing rate increases during proestrus-estrus in the rat.

Neuronal activity of the lateral septal nucleus (LSN) is related to motivational and hedonic behavior. Even though some changes in mood and anxiety during proestrus and pregnancy have been reported, the possible changes in the neuronal activity of the LSN through the phases of the estrous cycle are unknown. In the present study we explored the neuronal activity from the LSN using glass micropipettes (NaCl 1 M, and Evans blue 2.5%; 3-8 Mohms in 30 urethane (1 g/kg) anesthetized Wistar rats. Analysis of data included a total of 88 single-unit extracellular recordings taken from the LSN during proestrus (n = 22), estrus (n = 23), diestrus (n = 22), and metestrus (n = 21). The highest values of firing rate were found in proestrus, and the lowest in metestrus, F(3,84) = 3.78, p < 0.01. During estrous cycles, in the phase characterized by high plasma levels of estradiol and progesterone, i.e., proestrus-estrus, the neurons from the dorsal aspect of the LSN fired at significantly (p < 0.05) higher frequencies, shorter first-order intervals and a lower coefficient of variation than those in the phase characterized by lower levels of estradiol and progesterone (metestrus-diestrus). In another group of rats (n = 12), immobility in the forced-swim test was assessed. Consistently, a longer latency (p < 0.05) for the first period of immobility and a nonsignificant trend to a lowered total time in immobility were found in proestrus and estrus. It is concluded that the higher firing rate in neurons from the dorsal aspect of the LSN during proestrus-estrus, may be associated with an increased motivation to escape from a stressful situation.

Affect↗

PubMed2000

Interaction of desipramine with steroid hormones on experimental anxiety.

The present study analyzes if estradiol benzoate and/or progesterone interact with desmethylimipramine (DMI) to diminish experimental anxiety. The animal model of anxiety used was the conditioned defensive burying test. Dose response curves for DMI (0.625, 1.25 and 2.5 mg/kg, every 24 h, during 21 days), estradiol benzoate (0.5, 1.0, 2.0 and 4.0 micrograms/rat, 48 h) and progesterone (0.5, 1.0 and 2.0 mg/rat, -4 h) were made in ovariectomized rats. DMI per se decreased dose dependently the cumulative burying time, an effect considered as anxiolytic-like. Progesterone produced a decrease in burying at the highest dose, while estradiol benzoate had no effect on defensive burying. Both, progesterone (0.5 mg/rat) and estradiol benzoate (4.0 micrograms/rat) were able to decrease the cumulative burying behavior when injected with a subthreshold dose of DMI (1.25 mg/kg). In addition, the effect of DMI (1.25 mg/kg) plus the combination of estradiol benzoate and progesterone, sequentially administered (48 h and 4 h before the tests, respectively), also produced a synergistic decrease in burying behavior. In general, the treatments produced no changes in burying behavior latency, neither in spontaneous ambulation or in nociception. It is concluded that DMI synergizes its anxiolytic-like effect when administered with estradiol alone or in combination with progesterone. Present data provide experimental evidence suggesting an interaction between hormones and antidepressants. Results are discussed on the basis of the interaction between steroids and serotonergic or GABAergic receptors.

Animals↗

PubMed2000

Purification and bioassays of a diuretic and natriuretic fraction from garlic (Allium sativum).

The intravenous administration of a purified fraction (6 microg/kg) to anaesthesized dogs was followed by a significant biphasic diuretic and natriuretic response which reached a maximum at 180 min after injection. Chloride, but not potassium ions, followed the natriuretic profile. No changes were observed in arterial blood pressure or in the electrocardiogram. The purified garlic fraction also induced an inhibitory dose-dependent effect on kidney Na, K-ATPase.

Allium↗

PubMed1999

Chronic treatment with desipramine induces an estrous cycle-dependent anxiolytic-like action in the burying behavior, but not in the elevated plus-maze test.

The effect of chronic desipramine (DMI, 2.5 mg/kg x 21-26 days) treatment in female rats in two anxiety paradigms was assessed: the burying behavior (BB) and the elevated plus-maze (EPM) tests. In the BB test DMI produced a significant decrease in burying in ovariectomized rats, an effect considered as anxiolytic-like. In cycling females, DMI also reduced the cumulative BB most notably in proestrus rats. However, in diestrus rats no anxiolytic-like actions were observed. In addition, DMI increased BB latencies in proestrus and estrus rats. In the EPM test, DMI produced anxiolytic-like actions only in ovariectomized rats, while no significant actions were found in cycling females. Finally, the chronic treatment with DMI produced a general reduction in the ambulatory behavior of rats in all estrous cycle phases. Results are discussed on the basis of the differences between both anxiety paradigms and the probable relationship between the steroids secreted during proestrus and chronic DMI treatment.

Analysis of Variance↗

PubMed1999

Sedative actions of Ternstroemia sylvatica in the male rat.

Ternstroemia sylvatica is a plant reputed popularly to possess a anxiolytic properties but has not yet been systematically tested for such activity. The behavioral actions of T. sylvatica were examined using the open field test, the elevated plus-maze test, and the forced swim test in male rats. T. sylvatica (7.1 mg/kg and 14.2 mg/kg, i.p.) reduced ambulatory behavior in the open field test and cancelled the anti-immobility actions produced by desipramine (32 mg/kg, i.p.) in the forced swim test, as did diazepam. In the elevated plus-maze test, T. sylvatica (7.1 mg/kg, i.p.) failed to show anxiolytic actions. It is concluded that Ternstroemia sylvatica produces sedative effects rather than the attributed anxiolytic actions.

Animals↗

PubMed1999

Mimosa pudica may possess antidepressant actions in the rat.

In Mexico, aqueous extracts from dried leaves of Mimosa puolica are employed to alleviate depression. In this study, the behavioral actions of aqueous extracts of M. pudica at various concentrations were tested. Rats having received saline (0.9%; 0.30 ml; I.P.), clomipramine, desipramine or several dosages of aqueous extracts from M. pudica (ml = 2.0 mg/kg; m2 = 4.0 mg/kg; m3 = 6.0 mg/kg; m4 = 8.0 mg/kg) during a 30-day period were submitted to the forced swimming test and to the test for differential reinforcement of low rates of response at 72 sec (DRL-72s). Any possible anxiolytic action resulting from several doses (ml = 2.0 mg/kg; m2 = 4.0 mg/kg; m3 = 6.0 mg/kg; m4 = 8.0 mg/kg) of extracts of M. pudica were compared with those caused by diazepam (1.3 mg/kg, I.P.) in the elevated plus-maze test. Results showed that clomipramine (1.25 mg/kg, I.P.), desipramine (2.14 mg/kg, I.P.) and M. pudica (6.0 mg/kg and 8.0 mg/kg, I.P.) reduced immobility in the forced swimming test and increased the rate of reinforcers received in the DRL-72s test; these data suggest that M. pudica produces antidepressant effects in the rat. Diazepam increased the open-arms exploration time in the elevated plus-maze test, but M. pudica did not show any comparable action at any tested dose. M. pudica therefore produced an antide-pressant-like profile similar to two tricyclic antidepressants.

Animals↗

PubMed1999

In vitro recoating of reovirus cores with baculovirus-expressed outer-capsid proteins mu1 and sigma3.

Reovirus outer-capsid proteins mu1, sigma3, and sigma1 are thought to be assembled onto nascent core-like particles within infected cells, leading to the production of progeny virions. Consistent with this model, we report the in vitro assembly of baculovirus-expressed mu1 and sigma3 onto purified cores that lack mu1, sigma3, and sigma1. The resulting particles (recoated cores, or r-cores) closely resembled native virions in protein composition (except for lacking cell attachment protein sigma1), buoyant density, and particle morphology by scanning cryoelectron microscopy. Transmission cryoelectron microscopy and image reconstruction of r-cores confirmed that they closely resembled virions in the structure of the outer capsid and revealed that assembly of mu1 and sigma3 onto cores had induced rearrangement of the pentameric lambda2 turrets into a conformation approximating that in virions. r-cores, like virions, underwent proteolytic conversion to particles resembling native ISVPs (infectious subvirion particles) in protein composition, particle morphology, and capacity to permeabilize membranes in vitro. r-cores were 250- to 500-fold more infectious than cores in murine L cells and, like virions but not ISVPs or cores, were inhibited from productively infecting these cells by the presence of either NH4Cl or E-64. The latter results suggest that r-cores and virions used similar routes of entry into L cells, including processing by lysosomal cysteine proteinases, even though the former particles lacked the sigma1 protein. To examine the utility of r-cores for genetic dissections of mu1 functions in reovirus entry, we generated r-cores containing a mutant form of mu1 that had been engineered to resist cleavage at the delta:phi junction during conversion to ISVP-like particles by chymotrypsin in vitro. Despite their deficit in delta:phi cleavage, these ISVP-like particles were fully competent to permeabilize membranes in vitro and to infect L cells in the presence of NH4Cl, providing new evidence that this cleavage is dispensable for productive infection.

Animals↗

PubMed1998

Binding site for S-adenosyl-L-methionine in a central region of mammalian reovirus lambda2 protein. Evidence for activities in mRNA cap methylation.

One or more proteins in mammalian reovirus core particles mediate two RNA methylation activities, (guanosine-7-N)-methyltransferase and (guanosine-2'-O)-methyltransferase, that contribute to forming the 5' cap 1 structure on viral mRNA. We used UV irradiation to identify core proteins that bind S-adenosyl-L-methionine (SAM), the methyl-group donor for both methyltransferases. A [methyl-3H]SAM-binding site was observed among the reovirus lambda proteins; was shown to be specific by competition with low levels of S-adenosyl-L-homocysteine, the product of methyl-group transfer from SAM; and was subsequently localized to protein lambda2. lambda2 mediates the guanylyltransferase reaction in cap formation and was previously proposed to mediate one or both methylation reactions as well. SAM binding was demonstrated for both lambda2 in cores and lambda2 expressed in insect cells from a recombinant baculovirus. Using three different methods to cleave lambda2, a binding site for SAM was tentatively localized to a central region of lambda2, between residues 792 and 1100, which includes a smaller region with sequence similarity to the SAM-binding pocket of other methyltransferases. Alanine substitutions at positions 827 and 829 within this predicted binding region greatly reduced the capacity of baculovirus-expressed lambda2 protein to undergo UV cross-linking to SAM but had no effects on either the guanylyltransferase activity of this protein or its conformation as judged by partial proteolysis, suggesting that one or both of these residues is essential for SAM binding. Based on these findings, we propose that the two methyltransferase activities involved in mRNA capping by reovirus cores utilize a single SAM-binding pocket within a central region of lambda2.

Animals↗

PubMed1998

Desipramine restricts estral cycle oscillations in swimming.

1. Desipramine (DMI) is a tricyclic antidepressant which reduces the immobility in rats forced to swim; however, it is unknown whether estral cycle phases impinge on DMI actions on immobility in daily swimming tests during several weeks. 2. In female wistar rats, vaginal smears taken before testing defined four estral phases. Afterwards, the authors assessed the latency for the first period of immobility in five-min forced swim tests practiced on 21-day DMI (DMI group), 21-day washout saline given after a 21-day DMI treatment (washout-saline group), or non-treated rats (control group). 3. We observed a longer latency for the first period of immobility in proestrus-estrus from the control and washout-saline groups. The 21-day treatment with DMI (2.1 mg/kg i.p., once a day) significantly (p < 0.001) increased the latency by about 160% from control regardless of the estral cycle phase. 4. It is concluded that proestrus-estrus relates to increased struggling behavior. DMI enhances struggling behavior independently of hormonal state.

Animals↗

PubMed1996

Diuretic and natriuretic effects of chromatographically purified fraction of garlic (Allium sativum).

The intravenous administration of chromatographically purified fractions of garlic (2, 4 and 6 micrograms/kg dry weight) to anaesthetized rabbits elicits dose-dependent diuretic-natriuretic responses which reach a maximum 60 min after injection, and return to basal levels after 90 min. A gradual decrease in heart rate, but not in arterial blood pressure was observed during the course of the experimental periods. The electrocardiogram was not affected.

Animals↗

PubMed1996

Raphe-septal neurons changes in sensitivity to desipramine following an early septal lesion in the rat.

1. The electrophysiological responsivity to desipramine (DMI) applied by systemic or local route was tested in Wistar female rats submitted to a wide lesion in the lateral septal area on the 8th day after birth. 2. One year after a septal lesion, the dorsal raphe nucleus (DRN) stimulation produced an initial brief response in lateral septal and CA1/CA3 neurons. In the control and sham-lesion groups, most recordings showed only this initial brief response (non-late responding neurons); however, in the lesion group most of the recorded neurons showed an afterdischarge. 3. DMI (2.14 mg/kg, 21 days, i.p.) increased the firing rate in septal and CA1/CA3 non-late responding neurons. In the equivalent septal neurons from lesion group, DMI produced the inverse effect, i.e., a decreased firing rate. 4. In septal non-late responding neurons, DMI (2 mM; 10-15 nAmps, 0.5 sec) applied by microiontophoresis increased the firing rate only after long-term systemic DMI impregnation. The response to locally applied DMI did not occur in the lesion group even after long-term DMI treatment. 5. In conclusion, an early lateral septal lesion canceled the response of intermediate-dorsal septal neurons to DMI applied by systemic and local routes.

Animals↗

PubMed1995

The combination of several antidepressants is not synergistic on the firing of lateral septal neurons in the rat.

1. Three kinds of antidepressants (clomipramine, sleep deprivation, and electroconvulsive shock) increase the firing rate in the lateral septal neurons of the rat. 2. The acute combination of these treatments, however, did not produce added effects on firing rate of lateral septal neurons in the rat. 3. 24 hours of sleep deprivation blocked the actions of a single electroconvulsive shock. 4. It is concluded that the firstly applied treatment modifies the receptors sensitivity from the very beginning, thus blocking the action of a second treatment.

Animals↗

PubMed1995

An early lesion of the lateral septal nuclei produces changes in the forced swim test depending on gender.

1. Several pharmacological maneuvers in very young rats produce later changes resembling human depression. 2. Rats were submitted to a wide lesion in lateral septal region at 8th day after birth and forced to swim at maturity. 3. Male lesioned group showed the highest amount of immobility; whereas, female sham lesion group showed a greater response to treatments. 4. A gender-dependent sensitivity to early lateral septal nucleus lesions and to antidepressants are concluded.

Animals↗

PubMed1994

Electroconvulsive shock decreases excitatory responses to serotonin in the caudate nucleus of the rat.

1. The present study explored the changes on the firing rate of caudate neurons, and the response to serotonin locally applied in rats submitted to electroconvulsive shock. 2. Electroconvulsive shock diminished the firing rate of caudate neurons and blocked the excitatory response produced by serotonin in a small amount of serotonin-sensitive neurons. 3. Results are likely to be related with transient changes in the receptor's affinity and dissociation constants, which may impinge on immediate memory retrieval.

Animals↗