Pramipexole effects on startle gating in rats and normal men

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

Binding of Pramipexole to Extrastriatal Dopamine D2/D3 Receptors in the Human Brain: A Positron Emission Tomography Study Using 11C-FLB 457

The purpose of this study was to determine the binding sites of pramipexole in extrastriatal dopaminergic regions because its antidepressive effects have been speculated to occur by activating the dopamine D2 receptor subfamily in extrastriatal areas. Dynamic positron emission tomography (PET) scanning using 11C-FLB 457 for quantification of D2/D3 receptor subtype was performed on 15 healthy volunteers. Each subject underwent two PET scans before and after receiving a single dose of pramipexole (0, 0.125, or 0.25 mg). The study demonstrated that pramipexole significantly binds to D2/D3 receptors in the prefrontal cortex, amygdala, and medial and lateral thalamus at a dose of 0.25 mg. These regions have been indicated to have some relation to depression and may be part of the target sites where pramipexole exerts its antidepressive effects

Sex in the PAC: A hidden affair in dark septate endophytes?

<p>Abstract</p> <p>Background</p> <p>Fungi are asexually and sexually reproducing organisms that can combine the evolutionary advantages of the two reproductive modes. However, for many fungi the sexual cycle has never been observed in the field or <it>in vitro </it>and it remains unclear whether sexual reproduction is absent or cryptic. Nevertheless, there are indirect approaches to assess the occurrence of sex in a species, such as population studies, expression analysis of genes involved in mating processes and analysis of their selective constraints. The members of the <it>Phialocephala fortinii </it>s. l. - <it>Acephala applanata </it>species complex (PAC) are ascomycetes and the predominant dark septate endophytes that colonize woody plant roots. Despite their abundance in many ecosystems of the northern hemisphere, no sexual state has been identified to date and little is known about their reproductive biology, and how it shaped their evolutionary history and contributes to their ecological role in forest ecosystems. We therefore aimed at assessing the importance of sexual reproduction by indirect approaches that included molecular analyses of the mating type (<it>MAT</it>) genes involved in reproductive processes.</p> <p>Results</p> <p>The study included 19 PAC species and > 3, 000 strains that represented populations from different hosts, continents and ecosystems. Whereas <it>A. applanata </it>had a homothallic (self-fertile) <it>MAT </it>locus structure, all other species were structurally heterothallic (self-sterile). Compatible mating types were observed to co-occur more frequently than expected by chance. Moreover, in > 80% of the populations a 1:1 mating type ratio and gametic equilibrium were found. <it>MAT </it>genes were shown to evolve under strong purifying selection.</p> <p>Conclusions</p> <p>The signature of sex was found in worldwide populations of PAC species and functionality of <it>MAT </it>genes is likely preserved by purifying selection. We hypothesize that cryptic sex regularely occurs in the PAC and that further field studies and <it>in vitro </it>crosses will lead to the discovery of the sexual state. Although structurally heterothallic species prevail, it cannot be excluded that homothallism represents the ancestral breeding system in the PAC.</p

LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT2A receptor

Compounds that activate the 5-HT2A receptor, such as lysergic acid diethylamide (LSD), act as hallucinogens in humans. One notable exception is the LSD congener lisuride, which does not have hallucinogenic effects in humans even though it is a potent 5-HT2A agonist. LSD and other hallucinogens have been shown to disrupt prepulse inhibition (PPI), an operational measure of sensorimotor gating, by activating 5-HT2A receptors in rats. We tested whether lisuride disrupts PPI in male Sprague–Dawley rats. Experiments were also conducted to identify the mechanism(s) responsible for the effect of lisuride on PPI and to compare the effects of lisuride to those of LSD. Confirming a previous report, LSD (0.05, 0.1, and 0.2 mg/kg, s.c.) reduced PPI, and the effect of LSD was blocked by pretreatment with the selective 5-HT2A antagonist MDL 11,939. Administration of lisuride (0.0375, 0.075, and 0.15 mg/kg, s.c.) also reduced PPI. However, the PPI disruption induced by lisuride (0.075 mg/kg) was not blocked by pretreatment with MDL 11,939 or the selective 5-HT1A antagonist WAY-100635 but was prevented by pretreatment with the selective dopamine D2/D3 receptor antagonist raclopride (0.1 mg/kg, s.c). The effect of LSD on PPI is mediated by the 5-HT2A receptor, whereas activation of the 5-HT2A receptor does not appear to contribute to the effect of lisuride on PPI. These findings demonstrate that lisuride and LSD disrupt PPI via distinct receptor mechanisms and provide additional support for the classification of lisuride as a non-hallucinogenic 5-HT2A agonist

Mapping anhedonia onto reinforcement learning: A behavioural meta-analysis

BACKGROUND: Depression is characterised partly by blunted reactions to reward. However, tasks probing this deficiency have not distinguished insensitivity to reward from insensitivity to the prediction errors for reward that determine learning and are putatively reported by the phasic activity of dopamine neurons. We attempted to disentangle these factors with respect to anhedonia in the context of stress, Major Depressive Disorder (MDD), Bipolar Disorder (BPD) and a dopaminergic challenge. METHODS: Six behavioural datasets involving 392 experimental sessions were subjected to a model-based, Bayesian meta-analysis. Participants across all six studies performed a probabilistic reward task that used an asymmetric reinforcement schedule to assess reward learning. Healthy controls were tested under baseline conditions, stress or after receiving the dopamine D2 agonist pramipexole. In addition, participants with current or past MDD or BPD were evaluated. Reinforcement learning models isolated the contributions of variation in reward sensitivity and learning rate. RESULTS: MDD and anhedonia reduced reward sensitivity more than they affected the learning rate, while a low dose of the dopamine D2 agonist pramipexole showed the opposite pattern. Stress led to a pattern consistent with a mixed effect on reward sensitivity and learning rate. CONCLUSION: Reward-related learning reflected at least two partially separable contributions. The first related to phasic prediction error signalling, and was preferentially modulated by a low dose of the dopamine agonist pramipexole. The second related directly to reward sensitivity, and was preferentially reduced in MDD and anhedonia. Stress altered both components. Collectively, these findings highlight the contribution of model-based reinforcement learning meta-analysis for dissecting anhedonic behavior

Root-associated fungi of Vaccinium carlesii in subtropical forests of China: intra- and inter-annual variability and impacts of human disturbances

Ericoid mycorrhiza (ERM) are expected to facilitate establishment of ericaceous plants in harsh habitats. However, diversity and driving factors of the root-associated fungi of ericaceous plants are poorly understood. In this study, hair-root samples of Vaccinium carlesii were taken from four forest types: old growth forests (OGF), secondary forests with once or twice cutting (SEC I and SEC II), and Cunninghamia lanceolata plantation (PLF). Fungal communities were determined using high-throughput sequencing, and impacts of human disturbances and the intra- and inter-annual variability of root-associated fungal community were evaluated. Diverse fungal taxa were observed and our results showed that (1) Intra- and inter-annual changes in root-associated fungal community were found, and the Basidiomycota to Ascomycota ratio was related to mean temperature of the sampling month; (2) Human disturbances significantly affected structure of root-associated fungal community of V. carlesii, and two secondary forest types were similar in root-associated fungal community and were closer to that of the old growth forest; (3) Plant community composition, edaphic parameters, and geographic factors significantly affected root-associated fungal communities of V. carlesii. These results may be helpful in better understanding the maintenance mechanisms of fungal diversity associated with hair roots of ERM plants under human disturbances

Controlled release of carvacrol and curcumin: bio-based food packaging by synergism action of TEMPO-oxidized cellulose nanocrystals and cyclodextrin

International audienceOxidized cellulose nanocrystals with sodium carboxylate groups (TOCNC-COONa) and with free carboxyl groups (TOCN-COOH) were prepared and then chemically modified with beta-cyclodextrin (βCD) and hydroxypropyl-beta-cyclodextrin (HPβCD) to prepare materials able to load and release antibacterial molecules over a prolonged period of time. The materials were characterized by infrared spectroscopy, and the CD content of modified TOCNCs determined by phenolphthalein colorimetry. The extent of grafting was also assessed by QCM-D and microscopy was used to ascertain and compare the morphology of both TOCNC-COONa/HPβCD and TOCNC-COOH/HPβCD. Then, carvacrol and curcumin were entrapped by the attached HPβCD and their prolonged release confirmed, as compared to neat material. The combined effects of HPβCD and carvacrol on the antimicrobial properties of TOCNC-COOH films were finally evaluated