[Therapeutic applications of classical serotonergic psyche-delics: neurobiological mechanisms and neural networks]. / Therapeutische toepassingen van klassieke serotonerge psychedelica: neurobiologische mechanismes en neurale netwerken.

BACKGROUND: Psychedelics have received renewed scientific attention in recent decades because of their potential to induce long-term changes in behaviour and cognition with potential therapeutic applications in various psychiatric indications. AIM: To provide a brief overview of the neurobiological action of classical serotonergic psychedelics, their impact on neural networks and implications for potential clinical applications. METHOD: We provide a non-exhaustive review of the current literature by subsequently and thematically outlining: 1. the empirical evidence concerning the action of psychedelics on the level of individual neuronal cells; 2.their effects on the level of neural networks; and 3. their influence on neuroplasticity and 4. different mechanistic hypotheses about the potential therapeutic effects of psychedelic substances. We illustrate this through key studies that provided important historical breakthroughs and show how these findings were integrated into the current theories. RESULTS: Studies evidence the central role of 5-HT2A receptors for the subjective effects of psychedelics, as well as affinity for many other receptors. Through a complex cascade of downstream effects, psychedelic substances lead to dynamic changes in different neural circuits and increased neuroplasticity which potentially persists even after the subjective effects have subsided. Several theoretical concepts offer complementary explanations for the relationship between the effects at neurobiological and psychological levels. CONCLUSION: Although the underlying neurobiological mechanisms are not yet fully understood and methodological challenges remain, the current research offers valuable insights into how a single or a few administrations of a psychedelic substance could lead to symptom improvements that can last for weeks, months, or even longer, if used in a supportive setting and in combination with psychotherapy.

The Asp298Asn missense mutation in the porcine melanocortin-4 receptor ( MC4R) gene can be used to affect growth and carcass traits without an effect on meat quality.

A promising tool to improve daily gain in pigs is the missense mutation (Asp298Asn) in the melanocortin-4 receptor (MC4R) gene, especially in the Belgian pig industry where the slow-growing Piétrain breed is very frequently used as the sire breed. The MC4R is expressed in the appetite-regulating region of the brain where it regulates feed intake and energy balance. The mutation has been associated with differences in fatness, daily gain and feed intake. However, less information on the correlated effects on meat quality is available. In order to evaluate the influence of the MC4R mutation on carcass and meat quality parameters, a total of 1155 pigs of a four-way cross were slaughtered at an average live weight of 109 kg, and data about daily live-weight gain, carcass and meat quality were collected. Allelic frequencies were 0.69 for the G-allele (298Asp variant or well-conserved variant) and 0.31 for the A-allele (298Asn variant or the mutated variant). Barrows and gilts were almost equally distributed in this population with, respectively, 49.9% and 50.1%. Moreover, independent of this mutation, the relationship between average daily gain (ADG) and carcass on the one hand and meat quality traits on the other hand was evaluated in this population. A significant positive influence of the MC4R mutation on ADG (P < 0.001) was found, accompanied by a higher fat thickness (P < 0.05) and a lower carcass lean meat content (P < 0.01), whereas muscle thickness and carcass conformation traits were not affected. The effects on meat quality traits were not significant, except for a lower shear force (P = 0.054) and a higher intramuscular fat content (P = 0.052) in AA animals. In the longissimus, pH and pork quality meter (PQM) values were not influenced, and effects on drip loss and colour were not apparent. Residual correlation coefficients between ADG and carcass lean meat content on the one hand and meat quality traits on the other hand were generally very low (|r|>0.1). Higher ADG, higher carcass fat thickness and lower carcass lean meat content were correlated with slightly lower shear force values (|r|∼0.1, P < 0.05). In conclusion, in the studied population, the Asp298Asn mutation in the MC4R gene was associated with improved daily gain, higher carcass fatness and almost no effect on meat quality traits.

The feeding of ad libitum dietary protein to organic growing-finishing pigs.

The effects of three dietary protein levels on growth, meat, and carcass traits were studied in organic pigs fed a three-phase diet. Assuming lysine was the first limiting amino acid, feeds were formulated to ileal digestible (ID) lysine content, with the ID lysine:crude protein ratio set at a constant of 4%. Feeds were also formulated to an isocaloric rate (net energy: 9.4 MJ/kg during the first feeding phase, 9.25 MJ/kg during the second feeding phase and 9.1 MJ/kg during the finisher phase), with a high (HP), a medium (MP) or a low (LP) protein content ranging from 20% to 14% crude protein (CP). ID lysine content of the LP and MP feed was, respectively, 80% and 90% of the ID lysine content of the HP feed. The nutrient formulation of the HP feed was similar to nutrient levels commonly used in conventional Belgian pig farming. From 20 to 40 kg liveweight, the pigs showed better feed conversion ratios, with an increasing dietary protein concentration (r(2)=0.84). This effect was not observed in the second and third phases, although a significant effect of protein concentration on voluntary feed intake in the second phase did occur (P=0.018), probably as a compensation for the lower protein concentration in the LP diet. Analysis of the carcasses showed a lower meat percentage with lower protein concentration (P<0.05), whereas influences on meat quality were limited. It was concluded that whereas during the first phase of growth, higher protein concentration leads to better performance, from the second phase onwards (45 kg), at least with isocaloric diets, a decrease in protein content (corresponding to a 10% reduction in dietary ID lysine levels compared to conventional pig fattening) may be used in organic growing-finishing pig nutrition.

The estimated accuracy of the EU reference dissection method for pig carcass classification.

This experiment was designed to describe the accuracy of the EU-reference dissection method, and to describe the types of factors influencing the accuracy and assess their size. The experiment was conducted in four different European countries at two abattoirs within each country. A total of 128 carcasses was selected according to carcass weight, fat class and sex, and 8 butchers from different countries dissected the carcasses. Due to the experimental design of the experiment a variation in pig type was found between countries. The accuracy was expressed by the repeatability and reproducibility standard deviation, which were found to be 0.87 and 1.10, respectively, and by the reliability, found to be 0.87. This indicates a high accuracy, although a significant effect was found on the estimation of lean meat percentage (LMP) of butcher, and also that jointing of the carcass was of overall importance to the accuracy of the EU-reference dissection method.

The reduction of heat production in exercising pigeons after L-carnitine supplementation.

Four groups (CS,CR,PS,PR) of nine trained male racing pigeons were deprived of feed for 1 d and then subjected to a respiration chamber test in order to study the effect of oral 1-carnitine supplementation on the energy metabolism during flight. One week before, groups CS and CR were orally supplemented with 90 mg of 1-carnitine daily, whereas PS and PR were given a placebo. Groups CS and PS underwent flight simulation by electrostimulation of the breast muscles. Flight simulation increased heat production, kept respiratory quotient from decreasing, decreased thyroxine levels, and increased weight loss. L-Carnitine decreased the rise in heat production during electrostimulation but did not influence respiratory quotient, weight loss, or thyroid hormones. L-Carnitine supplementation in pigeons improves fatty acid combustion efficiency during heavy exercise.

The influence of dietary salt level on water consumption, farrowing, and reproductive performance of lactating sows.

During two consecutive lactations using a switch-back design, 16 sows received a corn, cassava, barley, and soybean meal diet supplemented with either 8.5 or 1 g/kg of NaCl (.4% Na or .1% Na, respectively). The average daily water consumption during the 4-wk lactation period was greater (P < .01) for the sows fed the high-salt diet than for those fed the low-salt diet (13.9 vs 12.4 L, respectively). Urine production accounted for 27% of the water intake during lactation. This resulted in a difference during the entire lactation period of 42.2 L in water consumption (P = .07) and 11.4 L in urine production (P = .07). The Na and Cl concentrations of the urine for sows fed the high-salt diet were higher than for sows fed the low-salt diet (P < .05), but the K, Mg, P, and Ca concentrations were not influenced. The milk composition, measured at d 1, 13, and 27 of lactation, was relatively independent of the dietary salt level, except for the Cl concentration at d 1 after farrowing, which was higher (P < .05) for sows fed the high-salt diet. The moisture and ash content of the milk increased with the length of the lactation, irrespective of the diet. The increased ash content on d 13 and 27 of lactation was accounted for by the increased concentrations of P and Ca. There was no effect of dietary salt level on weight change of the sow or on the growth performance of the pigs. The interval from weaning to estrus (n = 13, t = 2.48, P = .029) was shorter for sows fed the high-salt diet than for sows fed the low-salt diet (6.2 +/- 1.0 and 12.6 +/- 3.1 d, respectively). More sows were unsuccessfully mated after receiving the low-salt diet during lactation. These results indicate that a low-salt diet for lactating sows results in lower water consumption, lower urine production, and lower Na and Cl concentrations in the urine. Milk composition, weight change of the sow, and growth performance of the pigs were not altered, but reproductive failures afterward may point to a salt deficiency during lactation.