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Pramipexole effects on startle gating in rats and normal men.

ABSTRACT: Dopamine D3 receptors regulate sensorimotor gating in rats, as evidenced by changes in prepulse inhibition (PPI) of startle after acute administration of D3 agonists and antagonists. In this study, we tested the effects of the D3-preferential agonist, pramipexole, on PPI in normal men and Sprague-Dawley rats.Acoustic startle and PPI were tested in clinically normal men, comparing the effects of placebo vs. 0.125 mg (n = 20) or placebo vs. 0.1875 mg (n = 20) pramipexole, in double blind, crossover designs. These measures were also tested in male Sprague-Dawley rats using a parallel design [vehicle vs. 0.1 mg/kg (n = 8), vehicle vs. 0.3 mg/kg (n = 8) or vehicle vs. 1.0 mg/kg pramipexole (n = 8)]. Autonomic and subjective measures of pramipexole effects and several personality instruments were also measured in humans.Pramipexole increased drowsiness and significantly increased PPI at 120-ms intervals in humans; the latter effect was not moderated by baseline PPI or personality scale scores. In rats, pramipexole causes a dose-dependent reduction in long-interval (120 ms) PPI, while low doses actually increased short-interval (10-20 ms) PPI. Effects of pramipexole on PPI in rats were independent of baseline PPI and changes in startle magnitude.The preferential D3 agonist pramipexole modifies PPI in humans and rats. Unlike indirect DA agonists and mixed D2/D3 agonists, pramipexole increases long-interval PPI in humans, in a manner that is independent of baseline PPI and personality measures. These findings are consistent with preclinical evidence for differences in the D2- and D3-mediated regulation of sensorimotor gating.

SUBMITTER: Swerdlow NR

PROVIDER: S-EPMC2718192 | biostudies-other | 2009 Sep

REPOSITORIES: biostudies-other

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Project description:BackgroundThe aim of this work was to study the toxic effects and target organs of Mosla chinensis Maxim (MCM) in rats and provide theoretical basis for clinical medication.MethodsThe subchronic toxicity study was conducted on 60 male and female SD rats using the fixed-dose method for the treatment groups and 20 male and female SD rats for the control. At the subchronic toxicity study, the water extract of MCM with fixed doses of 0.2 g/kg/day, 2 g/kg/day, and 20 g/kg/day was administered for 90 days intragastric, and the control group was given the same amount of distilled water. After 90 days, the general conditions of the rats were observed. Assessment on safety of the extract was conducted by a subchronic toxicity test which mainly examined alteration occurrence in gut flora and urine metabolism.ResultsThere was no significant difference in physical signs, reactivity, and stool characteristics in the four groups. Compared with the control group, the number of red blood cells in the male 2 g/kg/day group and the female 0.2 g/kg/day group was significantly different (P < 0.05). The detection of serum biochemical indicators showed that MCM has an effect on liver and kidney function but has no physiological significance. The level of low-density lipoprotein in male rats was lower than that in the control group (P < 0.05). Compared with the control group, the blood glucose levels of female rats in the 0.2 g/kg/day, 2 g/kg/day, and 20 g/kg/day groups were significantly increased (P < 0.05). As far as the diversity of intestinal flora is concerned, feeding MCM for 90 days has an influence on the distribution of intestinal flora. The content of lactic acid bacteria increased, and the ratio of hard bacteria to Bacteroides (f/b) was also affected, but there was no significant difference.ConclusionsThese findings showed that the long-term intragastric administration of the MCM is safe to use within its dose recommendation. But it could have a slight effect on the metabolism of uric acid by changing the composition of intestinal flora and affecting the metabolism of tryptophan.

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Pramipexole effects on startle gating in rats and normal men.

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