Expression of alpha-synuclein is increased in the hippocampus of rats with high levels of innate anxiety.

A genomic region neighboring the alpha-synuclein gene, on rat chromosome 4, has been associated with anxiety- and alcohol-related behaviors in different rat strains. In this study, we have investigated potential molecular and physiological links between alpha-synuclein and the behavioral differences observed between Lewis (LEW) and Spontaneously Hypertensive (SHR) inbred rats, a genetic model of anxiety. As expected, LEW rats appeared more fearful than SHR rats in three anxiety models: open field, elevated plus maze and light/dark box. Moreover, LEW rats displayed a higher preference for alcohol and consumed higher quantities of alcohol than SHR rats. alpha-Synuclein mRNA and protein concentrations were higher in the hippocampus, but not the hypothalamus of LEW rats. This result inversely correlated with differences in dopamine turnover in the hippocampus of LEW and SHR rats, supporting the hypothesis that alpha-synuclein is important in the downregulation of dopamine neurotransmission. A novel single nucleotide polymorphism was identified in the 3'-untranslated region (3'-UTR) of the alpha-synuclein cDNA between these two rat strains. Plasmid constructs based on the LEW 3'-UTR sequence displayed increased expression of a reporter gene in transiently transfected PC12 cells, in accordance with in-vivo findings, suggesting that this nucleotide exchange might participate in the differential expression of alpha-synuclein between LEW and SHR rats. These results are consistent with a novel role for alpha-synuclein in modulating rat anxiety-like behaviors, possibly through dopaminergic mechanisms. Since the behavioral and genetic differences between these two strains are the product of independent evolutionary histories, the possibility that polymorphisms in the alpha-synuclein gene may be associated with vulnerability to anxiety-related disorders in humans requires further investigation.

Effects of microgram doses of haloperidol on open-field behavior in mice.

This study was designed to evaluate the effects of low doses of haloperidol on the open-field behavior of mice. A three-phase effect of haloperidol on the motor activity of mice was observed (depression, no effect, depression). This three-phase action was clear-cut in three experimental approaches (amphetamine-induced hyperactivity, and apomorphine- and bromocriptine-induced hypoactivity). A differential action of haloperidol on dopamine receptors mediating motor stimulation and motor depression was proposed. The present data indicate that considerably more attention should be paid to the novel behavioral and biochemical actions of neuroleptic drugs in the microgram dose range.

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.

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.

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.

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.

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)

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.

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.

Bone mineral density in familial amyloid polyneuropathy and in other neuromuscular disorders.

Neuromuscular diseases are a known risk factor for immobilization-induced osteoporosis. The aim of the study was to analyse bone mineral density (BMD) in patients with familial amyloid polyneuropathy (FAP) type I (Val30 Met) and to compare them with a population of patients with other neuromuscular disorders. We studied 24, ambulatory, neuromuscular patients, all men and premenopausal women. We included 12 FAP patients (GI) and 12 patients with other disorders (GII). Clinical data included age, sex, height, weight, alcohol intake, smoking, calcium intake, physical activity and history of fractures. Serum and urinary calcium, osteocalcin, bone alkaline phosphatase, parathyroid hormone, thyroid stimulating hormone and urinary N-telopeptide cross-linked type 1 collagen were determined in all patients. Bone mineral density of lumbar spine, hip and wrist were determined by dual energy X-ray absorptiometry scan. No statistical differences were found in clinical or analytic data between the two groups, except for body mass index and calciuria, which were lower in GI. In GI, 54.5% were osteoporotic, against 23.1% in GII (P = 0.04). Bone mineral density was lower in GI when compared with GII, and tended to decrease with disease duration. Decreased BMI and the early autonomic involvement in GI probably explain the results. The prevention and early treatment of osteoporosis, in FAP patients should be considered a priority.

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.

Synergism between toxin-gamma from Brazilian scorpion Tityus serrulatus and veratridine in chromaffin cells.

Toxin-gamma (Tgamma) from the Brazilian scorpion Tityus serrulatus venom caused a concentration- and time-dependent increase in the release of norepinephrine and epinephrine from bovine adrenal medullary chromaffin cells. Tgamma was approximately 200-fold more potent than veratridine judged from EC50 values, although the maximal secretory efficacy of veratridine was 10-fold greater than that of Tgamma (1.2 vs. 12 microg/ml of catecholamine release). The combination of both toxins produced a synergistic effect that was particularly drastic at 5 mM extracellular Ca2+ concentration ([Ca2+]o), when 30 microM veratridine plus 0.45 microM Tgamma were used. Tgamma (0.45 microM) doubled the basal uptake of 45Ca2+, whereas veratridine (100 microM) tripled it. Again, a drastic synergism in enhancing Ca2+ entry was seen when Tgamma and veratridine were combined; this was particularly pronounced at 5 mM [Ca2+]o. Veratridine induced oscillations of cytosolic Ca2+ concentration ([Ca2+]i) in single fura 2-loaded cells without elevation of basal levels. In contrast, Tgamma elevated basal [Ca2+]i levels, causing only small oscillations. When added together, Tgamma and veratridine elevated the basal levels of [Ca2+]i without causing large oscillations. Tgamma shifted the current-voltage (I-V) curve for Na+ channel current to the left. The combination of Tgamma with veratridine increased the shift of the I-V curve to the left, resulting in a greater recruitment of Na+ channels at more hyperpolarizing potentials. This led to enhanced and more rapid accumulation of Na+ in the cell, causing cell depolarization, the opening of voltage-dependent Ca2+ channels, and Ca2+ entry and secretion.

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

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

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

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