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R Frussa-Filho

Publications and source records attributed to R Frussa-Filho.

67 records · Page 4Linked to original sources

Effects of haloperidol, bromocriptine and amphetamine on the development of Ehrlich ascites carcinoma in mice.

We determined the effect of 13 days of treatment with 2.0 mg/kg haloperidol, 4.0 mg/kg bromocriptine or 2.0 mg/kg amphetamine on the number of tumor cells of mice bearing Ehrlich ascites carcinoma. The dopaminergic blocker significantly reduced the number of tumor cells of experimental mice, but the two dopamine-mimetic drugs used did not significantly affect tumor development. These results suggest that although neuroleptic drugs to inhibit Ehrlich ascites tumors, this effect does not seem to be related to changes in dopaminergic neuronal transmission.

Amphetamine↗

Effect of age on antinociceptive effects of elevated plus-maze exposure.

It has been suggested that anxiety may be a critical factor in certain forms of non-opioid environmental analgesia. Furthermore, age has been reported to increase the anxiety levels in rats as measured in the elevated plus-maze. In the present investigation 10 young (3 months), 10 middle-aged (14-16 months) and 10 old (28-30 months) male Wistar rats were tested by the tail withdrawal assay of nociception before (baseline), and at 0 (T1) and 10 (T2) min after a 5-min exposure to the elevated plus-maze apparatus. Only old rats presented an increase in tail withdrawal latencies after elevated plus-maze exposure, even though this effect was statistically significant only immediately after exposure to the apparatus (baseline = 2.5 +/- 0.3 s; T1 = 3.8 +/- 0.3 s; T2 = 3.3 +/- 0.4 s). The results indicate that exposure to the elevated plus-maze induces a rapidly reversed and age-dependent antinociception in rats. They are also consistent with the proposed greater sensitivity of old rats to anxiogenic effects of the plus-maze.

Aging↗

Anxiety-induced antinociception in the mouse.

It has been suggested that exposure to the elevated plus-maze (EPM) apparatus induces antinociceptive effects in mice as measured by the tail-flick assay, which are not blocked by the opiate antagonist naltrexone. The present study performed on 3-month old male EPM-M1 albino mice (12-14 animals per group) was designed to assess a) if exposure limited to the open or to the enclosed arm of the EPM would alter this effect; b) whether or not pharmacologically induced anxiety (1.0 mg/kg pentylenetetrazole, PTZ) would also reduce nociception; c) if exposure to the EPM would alter visceral pain, as measured by the abdominal contortion test. The simultaneous exposure to both the open and enclosed arms of the EPM, but not the exposure limited to each type of arm, led to statistically significant increases in tail withdrawal latencies (TWL). Indeed, 10 min after exposure to both arms, TWL values (mean +/- SEM) were 10.31 +/- 0.87 s as compared to a baseline value of 5.46 +/- 0.53 s. The acute administration of PTZ significantly increased TWL. Conversely, EPM-induced antinociception was not detected by the abdominal contortion test. These results confirm the existence of EPM-induced antinociceptive effects demonstrated by others and show that they may be influenced by multiple determinants.

Analgesia↗

Effects of age and isolation on the evolution of catalepsy during chronic haloperidol treatment.

Sixteen young (5 months) and 16 old (20-24 months) male Wistar rats, housed together or in individual cages were observed for cataleptic behavior 10, 20 and 30 days after the beginning of chronic haloperidol treatment (1.0 mg/kg, twice daily, for 30 days). Catalepsy was measured by the bar test. Age increased the duration of haloperidol-induced catalepsy of isolated and group-housed rats in the three observation sessions (old-isolated = 7.4 +/- 0.2; old-group housed = 7.5 +/- 0.1; young-isolated = 6.3 +/- 0.2; young-group housed = 6.8 +/- 0.2 In seconds in session 1, for example). Conversely, isolation did not modify the sensitivity to the cataleptic effect of haloperidol. Even more important, no differences in duration of haloperidol-induced catalepsy were observed among the three sessions for each group. The results indicate that under the experimental conditions employed the animals did not develop tolerance nor sensitization to haloperidol-induced catalepsy. In addition, neither age nor isolation modified the absence of effects of repeated haloperidol treatment on the catalepsy behavior of rats.

Aging↗

Effects of single and long-term droperidol administration on open-field and stereotyped behavior of rats.

The effects of single and long-term droperidol administration on rat open-field and apomorphine-induced stereotyped behavior were studied. A single dose of droperidol decreased dose dependently not only locomotion and rearing frequencies in the open-field but also the apomorphine effects. Long-term droperidol administration induced significant tolerance to all parameters of activity recorded in the open-field. Unlike other dopamine blockers, droperidol withdrawn from long-term droperidol administration wasn't able to increase rats' open-field parameters significantly. However, like other dopamine blockers, droperidol withdrawn produced an augmented responsiveness to apomorphine-induced stereotyped behavior. These results suggest that the supersensitivity of central dopamine receptors developed after droperidol treatment may have peculiar characteristics.

Animals↗

Antitumor effects of dopaminergic blockers in mice bearing Ehrlich tumors.

We determined the effect of 13 days of treatment with 2.0 mg/kg haloperidol, 30.0 mg/kg metoclopramide or 4.0 mg/kg domperidone on the number of tumor cells of mice bearing Ehrlich ascites carcinoma. The three dopaminergic blockers significantly reduced the number of tumor cells of experimental mice. The mean +/- SEM number of tumor cells x 10(6)/ml saline lavage was 25.5 +/- 5.9 for the haloperidol group, 36.8 +/- 4.7 for the metoclopramide group, 25.3 +/- 3.5 for the domperidone group and 54.0 +/- 9.0 for the control mice (treated with 0.9% NaCl). In a second experiment, treatment with 0.5 and 2.0 mg/kg haloperidol showed that the antitumor effect of this drug was dose dependent. The possible mechanisms underlying these results (such as an increase in prolactin levels or a direct action of these drugs on lymphocytes) are discussed in light of the specific pharmacological properties of each dopaminergic blocker.

Analysis of Variance↗

Evaluation of memory and anxiety in rats observed in the elevated plus-maze: effects of age and isolation.

Twenty young (5 months) and 20 old (20-24 months) male Wistar rats, isolated or group housed, were tested in the elevated plus-maze to evaluate memory and anxiety. Memory was quantified by transfer latency (the time it took for the rat to move from the open arm to the enclosed arm) and anxiety by percent entries into the open arms. Isolation decreased the transfer latency of old (session 1 = 119.33 +/- 0.44 s; session 3 = 49.67 +/- 12.12 s) and young (session 1 = 111.20 +/- 8.80 s; session 3 = 55.90 +/- 13.60 s) rats, but did not modify percent entries into the open arms (old-isolated = 5.56 +/- 5.56; old-group housed = 10.18 +/- 7.05; young-isolated = 35.16 +/- 8.98; young-group housed = 33.21 +/- 8.11). Conversely, aging decreased percent entries into the open arms but did not affect the transfer latency of isolated or group-housed animals. The results indicate that the plus-maze test, unlike other methods for memory evaluation, does not discriminate between young and old rats. They also suggest that age increases anxiety and that isolation increases memory levels, but that there is no interaction between age and isolation with regard to their effect on memory and anxiety in rats.

Age Factors↗

Effects of single and long-term administration of sulpiride on open-field and stereotyped behavior of rats.

1. The effects of single (3.0 to 180.0 mg/kg) and long-term (up to 90.0 mg/kg) administration of sulpiride on open-field and apomorphine-induced stereotyped behavior of rats were studied. 2. When animals were studied 30 min after ip sulpiride administration, locomotion and rearing frequencies in the open-field or apomorphine effects were not modified in a dose-dependent and consistent way by the single sulpiride administration. 3. In relation to control values, a significant decrease in apomorphine-induced stereotyped behavior was observed when rats were injected with a single sulpiride dose 2.5, 5.0, 7.5 and 10.0 h before the dopaminergic agonist. 4. Withdrawal from long-term ip sulpiride administration (up to 90.0 mg/kg per injection, twice daily for 57 days) induced a significant increase in all parameters of activity recorded in the open-field, and the responsiveness to apomorphine was also augmented in sulpiride-withdrawn rats. 5. These results suggest that sulpiride, a benzamide drug that differs from classic neuroleptic agents by producing fewer extrapyramidal side effects, also induces supersensitivity of central dopaminergic receptors.

Animals↗

Effects of single and long-term metoclopramide administration on open field and stereotyped behavior of rats.

The effects of single and long-term metoclopramide administration on rat open-field and apomorphine-induced stereotyped behavior were studied. A single dose of metoclopramide decreased dose dependently not only locomotion and rearing frequencies in the open field but also the apomorphine effects. Withdrawal from long-term metoclopramide administration induced a significant increase in all parameters of activity recorded in the open field. The responsiveness to apomorphine was also augmented in metoclopramide-withdrawn rats. These results were considered to be a consequence of the supersensitivity of central dopaminergic receptors.

Animals↗

Differential effects of single and long-term amphetamine and apomorphine administrations on locomotor activity of rats.

The effects of single and long-term administration of apomorphine (AP) and amphetamine (AM) on the locomotor behaviour of rats observed in an open-field (LF), and on the locomotion stereotyped behaviour (LSB) of rats were compared in the present study. Single AP treatment did not modify LF and LSB. Single AM treatment reduced the duration of LSB 2 and 3 days after drug administration, but did not alter the LF. Long-term treatment with both drugs reduced the inhibitory effects of low AP doses on open-field behaviour. Subsensitivity of dopaminergic autoreceptors induced by the long-term dopaminergic agonist administration was considered to be involved in the differences observed.

Amphetamine↗

Effect of ganglioside (GM1) on memory in senescent rats.

Monosialoganglioside GM1 (GM1) has been found to alleviate genetic and lesion-induced memory deficits. The purpose of this study was to investigate the effects of 7-day treatment with GM1 (50 mg/kg IP) on acquisition and retention performance of senescent rats in a passive avoidance situation. Saline-treated old rats showed a decreased performance in acquisition and retention tests as compared to saline-treated adult rats. GM1 improved both acquisition and retention performance of old animals, and there was no significant difference between GM1-treated old rats and saline-treated adult rats. These data suggest that GM1 treatment can improve memory deficits in intact senescent animals.

Aging↗

Effects of age on a new animal model of tardive dyskinesia.

The effects of age were studied on a new animal model of tardive dyskinesia, i.e., the quantification of oral dyskinesia in rats repeatedly treated with reserpine. Adult and old rats received two injections of reserpine (0.5 or 1.0 mg/kg s.c.) or vehicle, separated by 48 h. One, 10, 25 and 40 days after the second injection of reserpine or vehicle, the animals were observed for quantification of the behavioral parameters of oral dyskinesia: tongue protrusion and vacuous chewing movement frequencies and duration of twitching of the facial musculature. Phenomenologically, control old rats and reserpine-treated adult animals showed very similar oral dyskinesia. When compared to control adult rats, the significant increase in tongue protrusion frequency induced by reserpine treatment was more persistent in the old rats than in the adult animals. Because it is well known that age increases the persistence of tardive dyskinesia, our data provide further support for the validation of reserpine-induced oral dyskinesia as an animal model of tardive dyskinesia. In addition, the possibility is raised that a common pathophysiological mechanism may underlie tardive dyskinesia and age- and reserpine-induced oral dyskinesia.

Aging↗

Effects of dopaminergic agents on visceral pain measured by the mouse writhing test.

The present study explored the role of the dopaminergic transmission in the mouse writhing test analgesia by examining the relative analgesic activity of indirect dopaminergic agonists (amphetamine and cocaine), a mixed D1/D2 direct agonist (apomorphine), and a direct D1 (SKF38393) and D2 (bromocriptine) dopaminergic agonist. Amphetamine (1, 3 and 10 mg/kg, s.c.), cocaine (3 and 10 mg/kg, s.c.), apomorphine (0.3, 1 and 3 mg/kg, s.c.) and bromocriptine (30 mg/kg, s.c.) induced a significant decrease of the number of writhes. SKF38393 (1, 3, 10 and 30 mg/kg, s.c.) had no effect on writhing. The antinociceptive effect of amphetamine and cocaine was not reversed by naltrexone, haloperidol or SCH23390. The apomorphine- and bromocriptine-induced analgesia was not reduced by naltrexone or SCH23390 but was attenuated by haloperidol; the apomorphine-induced analgesia was not modified by domperidone. The present results suggest an involvement of the dopaminergic transmission in visceral nociception. This dopaminergic component appears to involve exclusively the central D2 receptor system, and does not seem to be influenced by opioid mechanisms.

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