Effect of withdrawal from long-term nifedipine administration on open-field habituation in the rat

The effects of withdrawal from long-term administration of nifedipine (2.5 mg/kg, ip, twice daily for 30 days) on open-field habituation were evaluated in 3-month old male Wistar rats (13-14 animals per group). Habituation was evaluated by the ratio between locomotion or rearing frequencies obtained in the second and the first open-field session for each animal. Nifedipine treatment did not modify the locomotion ratio (with a mean +/- SEM ratio of 0.66 +/- 0.12 for control and 0.45 +/- 0.08 for nifedipine-treated group) nor the rearing ratio (with a mean +/- SEM ratio of 0.51 +/- 0.12 for control and 0.62 +/- 0.18 for nifedipine-treated group). The possible factors underlying the discrepancy between the present results and the commonly reported positive effects of calcium channel blockers on memory are discussed.

Effects of single and long-term administration of nifedipine on nociception and stereotyped behavior of rats

In the present investigation, nociception and stereotyped behavior were evaluated in 3-month old male Wistar rats after a single nifedipine dose (2.5 and 5.0 mg/kg, ip, 1 h before testing, 6-7 rats per group for stereotypy studies and 15 animals per group for nociception experiments) or after long-term nifedipine treatment (2.5 mg/kg, ip, twice daily for 30 days, with testing performed 72 or 96 h after the last injection, 7 rats per group for stereotypy studies and 14-16 animals per group for nociception experiments). Stereotypy was induced with 2.5 mg/kg amphetamine, ip, and nociception was measured by the tail-immersion test. Administration of a single nifedipine dose did not modify nociception or amphetamine-induced stereotypy (with a mean +/- SEM tail-withdrawal latency of 4.5 +/- 0.5 s for control, 4.4 +/- 0.3 s for 2.5 mg/kg nifedipine and 4.7 +/- 0.7 s for 5.0 mg/kg nifedipine and with mean +/- SEM sum of stereotypy scores of 32.5 +/- 1.6 for control, 29.1 +/- 1.0 for 2.5 mg/kg nifedipine and 29.1 +/- 1.6 for 5.0 mg/kg nifedipine). Withdrawal from long-term nifedipine treatment did not affect stereotyped behavior (with mean +/- SEM sum of stereotypy scores of 28.7 +/- 1.6 for control and 30.7 +/- 1.3 for nifedipine-treated rats) but significantly increased tail-withdrawal latencies (with a mean +/- SEM tail-withdrawal latency of 4.1 +/- 0.3 s for control and 6.4 +/- 0.6 s for nifedipine-treated rats). Therefore, long-term nifedipine treatment induced plastic modifications in nociception but not in stereotyped behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of single and long-term administration of nifedipine on dopamine-related behaviors

The effects of single (2.5 and 5.0 mg/kg) and long-term (2.5 mg/kg, twice daily, for 30 days) ip administration of nifedipine on open-field and apomorphine-induced stereotyped behavior were evaluated in young male Wistar rats (12-16 animals per group for the open-field studies and 7 animals per group for the stereotypy experiments). Administration of a single dose of nifedipine produced no changes in ambulation or rearing frequencies or in immobility duration in the open-field compared to controls. Similarly, treatment with a single dose of nifedipine did not modify apomorphine-induced stereotypy. Withdrawal from long-term nifedipine administration caused a significant increase only in rearing frequency 24 h after the last drug injection (with a mean +/- SEM frequency of 23.2 +/- 2.8 for the nifedipine group and of 14.7 +/- 2.0 for control rats, after 6-min observation). This enhancement of rearing frequency was no longer observed 48 h after abrupt nifedipine withdrawal (means +/- SEM: 15.0 +/- 2.2 and 19.6 +/- 2.7 for nifedipine-treated and control rats, respectively). The other open-field behavioral parameters and apomorphine-induced stereotypy (which was observed 96 h after nifedipine withdrawal) were not affected by long-term nifedipine treatment; for example, the sum of stereotypy scores (mean +/- SEM) was 26.9 +/- 3.0 for nifedipine-treated rats and 25.5 +/- 2.2 for vehicle-treated animals. The possible mechanisms underlying these results are discussed in light of the changes in dopaminergic neurotransmission induced by dihydropyridine calcium channel blockers

Evaluation of memory in an elevated T maze: a comparison between spontaneously hypertensive, Wistar-Kyoto and Wistar EPM-1 rats

Four-month old male spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Wistar EPM-1 (EPM-1) rats (14-15 animals per group) were tested in an elevated T maze to evaluate memory. Blood pressures of SHR were hyper at the time of experiment (200-235 mmHg). The elevated T maze used consisted of an open arm at right angles with two enclosed arms elevated 50 cm above the ground. Memory was quantified by the escape latency ratio (the ratio of the time it took for the rat to move from the open arm to one of the enclosed arms in the second session to that in the first session) and by the inhibitory avoidance latency (time from being placed at the end of an enclosed arm to move to the open arm, in a 3rd session). No significant differences in escape latency ratios were observed among SHR, WKY and EPM-1 rats. Conversely, SHR presented a significant reduction in inhibitory avoidance latency as compared to those of WKY and EPM-1 rats (mean +/- SEM latency: 65.9 +/- 18.4 s for SHR, 129.9 +/- 21.8 s for WKY animals and 181.2 +/- 11.2 s for EPM-1 rats). These data were discussed in light of the known lowered reaction to aversive environments exhibited by SHR, as compared to WKY and EPM-1 rats

Comparison of anxiety measured in the elevated plus-maze, open-field and social interaction tests between spontaneously hypertensive rats and Wistar EPM-1 rats

On the basis of open-field and plus-maze results it has been proposed that spontaneously hypertensive (SHR) rats are less emotionally reactive than their normotensive controls, Wistar-Kyoto (WKY). However, the proposed anxiolytic characteristics of SHR rats may be questioned in view of the significant hypoactivity presented by WKY rats. In the present study, the behavioral response of spontaneously hypertensive (SHR) and equally active normotensive Wistar EPM-1 (EPM-1) rats (4-month old males, 10-13 animals per group) were evaluated in the open-field, social interaction and elevated plus-maze tests. In the open-field study, no differences were observed for total locomotion frequency and immobility duration, but SHR rats presented a higher central square locomotion frequency (23.8 +/- 2.1 vs 10.3 +/- 1.6) as compared to EPM-1. SHR rats also exhibited a greater duration of social interaction when compared to EPM-1 rats (mean +/- SEM values were 113.9 +/- 8.7 s for SHR vs 72.7 +/- 8.6 s for EPM-1 rats after 8-min observation). In the elevated plus-maze test, SHR rats presented an increased percent of entries (52.8 +/- 3.3 vs 28.3 +/- 4.5) and time in the open arms (65.6 +/- 6.0 vs 11.1 +/- 1.9) as compared to EPM-1 rats, although the total number of arm entries (9.2 +/- 0.9 vs 9.7 +/- 1.0) was unchanged. These results suggest that the anxiolytic behavior of SHR rats in relation to normotensive controls is not related to differences in motility levels

Effects of a single administration of buspirone on catalepsy, yawning and stereotypy in rats

In the present study, the effects of a single administration of buspirone (0.1, 0.3, 1.0, and 3.0 mg/kg sc-30 min before testing) on three dopamine-related behaviors were evaluated in 4-month old male Wistar rats (7-10 animals per group). Buspirone decreased haloperidol (2.0 mg/kg ip)-induced catalepsy in a dose-dependent manner (from 7.30 to 5.09 1n of s compared to the untreated control group). Apomorphine (0.06 mg/kg sc)-induced yawning was also dose-dependently reduced (from 26.7 to 0.9 yawns in 30 min) and so was apomorphine (1.0 mg/kg sc)-induced stereotypy (from 32.9 to 5.9, sum of scores). The present results indicate that buspirone presents unique pharmacological effects related to dopaminergic transmission not only in biochemical but also in behavioral terms

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-age (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(T) 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 ñ 0.3 s; T1 = 3.8 ñ 0.3s; T2 = 3.3 ñ 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

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 a) if exposure limited to the open or 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 nociceptions: 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 (means ñ SEM) were 10.31 ñ 0.87 s as compared to a baseline value of 5.46 ñ 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 multiple determinants