The regulatory function of Blastocystis spp. on the immune inflammatory response in the gut microbiome.

Blastocystis spp. is a unicellular organism that resides in digestive tract of various vertebrates, with a worldwide distribution and a variable prevalence. For many years, Blastocystis spp. was considered a cyst of a flagellate, a fungus, or a saprophyte yeast of the digestive tract; in 1996, it is placed in the group of stramenopiles (heterokonts). Since its new classification, many questions have arisen around this protist about its role as a pathogen or non-pathogen organism. Recent evidence indicates that Blastocystis spp. participates in the immune inflammatory response in the intestinal microbiome generating an anti-inflammatory response, showing a lower concentration of fecal inflammatory markers in infected human hosts. Here, we review recent findings on the regulatory function of Blastocystis spp. in the immune inflammatory response to comprehend the purpose of Blastocystis spp. in health and disease, defining if Blastocystis spp. is really a pathogen, a commensal or even a mutualist in the human gut microbiome.

Rapid development of semistarvation-induced hyperactivity in Dark Agouti rats. Excessive wheel running and effect of 3,4-methylenedioxymethamphetamine (MDMA).

Clinical studies have found that patients with anorexia develop high activity levels. These data suggest a possible implication of activity in the aetiology of anorexia and are in line with findings obtained in animals during experimental procedures to model interactions between activity and weight loss. Activity-based anorexia (ABA) and semistarvation-induced hyperactivity (SIH) develop when laboratory rats have food access restricted to a single period in the day and are given free access to an activity wheel. This experiment sought to show the effect on weight loss of the excessive activity normally seen in Dark Agouti rats and of hyperactivity induced by 3,4-methylenedioxymethamphetamine (MDMA). To this end, 32 female rats of the Dark Agouti strain were selected and divided into four groups in accordance with a 2 × 2 factorial design, in which one factor was treatment (saline or MDMA) and the other was access or lack of access to an activity wheel. Animals with wheel running access displayed a marked increase in running combined with accelerated weight loss. Although pharmacological treatment resulted in no observable effect on weight loss, rats treated with 12.5mg/kg MDMA generally registered more wheel running than did those treated with saline. Analysis of data on the temporal distribution of wheel running revealed an alteration in circadian activity patterns as a consequence of MDMA. These results, by showing a general high level of wheel running in Dark Agouti rats, once again emphasise the close relationship between activity and weight loss in the development of SIH and related phenomena such as ABA.

Response-food delay gradients for lever pressing and schedule-induced licking in rats.

Eight food-deprived Wistar rats developed stable patterns of lever pressing and licking when exposed to a fixed-time 30-s schedule of food pellet presentation. The rats were trained to lever press by presenting the lever 10 s before the programmed food delivery, with the food pellet being delivered immediately upon a lever press. The operant contingency was then removed and the lever was inserted through the entire interfood interval, being withdrawn with food delivery and reinserted 2 s later. On successive phases of the study, a protective contingency postponed food delivery if responses (lever presses or licks) occurred within the last 1, 2, 5, 10, 20, or 25 s of the interfood interval. Lever pressing was reduced at much shorter response-food delays than those that reduced licking. These results demonstrate that reinforcement contributes to the maintenance of different response patterns on periodic schedules, and that different responses are differentially sensitive to delays.

The effects of food presentation at regular or irregular times on the development of activity-based anorexia in rats.

Activity-based anorexia occurs when food availability is restricted to 1h of the day and a wheel is freely available to the rest of the time. Under such conditions rats run excessively and stop eating even during periods in which food is available. A defining characteristic of the excessive activity is that there is a peak of running in the anticipation of food availability. The present study was designed to test whether the occurrence of the food period at different times of the light phase of the light-dark cycle (from 08:00 to 20:00h) could impede or postpone the normal development of activity anorexia. We compared the effect of presenting the food at a fixed time of the light period with presenting it on a variable schedule. Far from impeding or postponing the development of activity-based anorexia, presenting food at irregular times resulted in a pronounced body-weight loss, a low food intake and an increase in locomotor activity. Animals ran excessively, with a peak at the start of the dark period, and again when lights were turned on in the experimental room (running in the anticipation of food). Both fixed and variable schedules of food availability resulted in the development of activity-based anorexia in rats.

Behavioural and pharmacological specificity of the effects of drugs on punished schedule-induced polydipsia.

Wistar rats were exposed to a multiple fixed-time 30-s food delivery schedule, with an on/off tone signalling the two components. Animals were matched in accordance with the levels of schedule-induced polydipsia. Drinking was then punished in one of the components: half of the rats received lick-dependent 10-s signalled delays and the other half lick-dependent electric shocks. The intensities of the shocks were adjusted to reduce behaviour by the same amount as the delays in food presentation. Unpunished components were used as yoked-control conditions, by presenting delays or shocks independently of the animals' behaviour. D-Amphetamine (0.3-2.0 mg/kg) and cocaine (1.0-10.0 mg/kg) dose-dependently increased (although only slightly) and then decreased schedule-induced polydipsia punished with lick-dependent delays in food presentation, a result not observed in control conditions or when the behaviour was suppressed by lick-dependent electric shocks. Diazepam (1.0-17.0 mg/kg) and pentobarbital (3.0-17.0 mg/kg) dose-dependently increased and then decreased only the schedule-induced drinking punished with lick-dependent shocks. Buspirone (0.1-1.0 mg/kg) and morphine (2.0-5.6 mg/kg) showed either no specific effects or further suppressed schedule-induced drinking. Results of these and previous experiments suggest that the antipunishment effects of drugs depend not only on the precise nature of the drug, but also on the manner in which the behaviour is maintained.

Level of response suppression and amphetamine effects on negatively punished adjunctive licking.

The purpose of the present study was to investigate whether the level of response suppression is a major determinant of the effect of D-amphetamine on negatively punished adjunctive drinking. Rats were initially exposed to a multiple fixed-time (FT) 30-s FT 30-s food delivery schedule. They were then divided into two groups and subjected to one of two different multiple schedules, FT 30-s FT 45-s or FT 30-s FT 90-s. The FT 45-s and FT 90-s components were signalled by a tone. Comparably high levels of adjunctive licking were observed in both FT 30-s components, intermediate licking levels in the FT 45-s component, and little licking in the FT 90-s component. Licking during the FT 30-s components was subsequently punished by lick-contingent signalled delays (by a blackout) in food delivery. The duration of such delays was adjusted to reduce licking to levels obtained in the FT 45-s or FT 90-s components, respectively for each of the two groups. Punished licking was increased by 0.3 and 1.0 mg/kg of D-amphetamine, an effect that was greater in the FT 30-s FT 90-s group. No increase in licking was observed in the FT 45-s component, but the 1.0 mg/kg dose also increased responding in the FT 90-s component. In general, no statistically significant differences were found between the effects of D-amphetamine on punished and unpunished schedule-induced licking. As licking decreased during the FT 90-s component when the punishment contingency was introduced in the alternate component, the punishment procedure and FT 30-s component were entirely removed. On this occasion, D-amphetamine failed to increase licking induced by the FT 90-s schedule. These results indicate that the level of response suppression might be a good indicator of the degree to which D-amphetamine shows antipunishment effects on adjunctive licking reduced by negative punishment procedures.

Amphetamine increases schedule-induced drinking reduced by negative punishment procedures.

RATIONALE: d-Amphetamine has been reported to increase schedule-induced drinking punished by lick-dependent signalled delays in food delivery. This might reflect a drug-behaviour interaction dependent on the type of punisher, because no such effect has been found when drinking was reduced by lick-contingent electric shocks. However, the anti-punishment effect of amphetamine could be mediated by other behavioural processes, such as a loss of discriminative control or an increase in the value of delayed reinforcers. OBJECTIVES: To test the effects of d-amphetamine on the acquisition and maintenance of schedule-induced drinking reduced by unsignalled delays in food delivery. METHODS: Rats received 10-s unsignalled delays initiated by each lick after polydipsia was induced by a fixed-time 30-s food reinforcement schedule or from the outset of the experiment. Yoked-control rats received these same delays but independently of their own behaviour. d-Amphetamine (0.1-3.0 mg/kg) was then tested IP. RESULTS: d-Amphetamine dose-dependently increased and then decreased punished schedule-induced drinking. The drug led to dose-dependent reductions when the delays were not contingent or when they were applied from the outset of training. CONCLUSIONS: These results support the contention that d-amphetamine has an increasing effect on schedule-induced drinking that has been previously reduced by a negative punishment procedure. This effect cannot be attributed to other potentially involved processes, and therefore support the idea that drug effects on punished behaviour depend on punishment being delays in food or shock deliveries.