Short communication: Mammary gland tight junction permeability after parturition is greater in dairy cows with elevated circulating serotonin concentrations

After parturition, the start of copious milk production in dairy cows requires the closure of tight junctions (TJ) to form the blood–milk barrier and prevent paracellular transfer of blood constituents into milk [e.g., lactate dehydrogenase (LDH) and serum albumin (SA)] and vice versa [e.g., appearance of α-lactalbumin (α-LA) in blood]. Serotonin (5-HT) has been demonstrated to alter tight junction permeability in the mammary gland. The present study investigated individual differences of TJ permeability of mammary epithelium at the beginning of lactation in relation to circulating 5-HT in dairy cows. Blood and milk samples were obtained from 11 multiparous Holstein dairy cows for the first time at 4 h after parturition, at the following 5 milkings, and at the evening milkings on d 5, 8, 10, and 14 of lactation. Retrospectively, cows were split into 2 groups according to their calculated areas under the curve of serum 5-HT during the entire experimental period: a high-serum 5-HT (HSS) group (5 cows) and a low-serum 5-HT (LSS) group (6 cows). The areas under the curve of serum 5-HT concentrations over the 324-h experimental period were 62 ± 2 × 10³ ng/mL in HSS and 25 ± 5 × 10³ ng/mL in LSS. Plasma α-LA concentration was greater in LSS than in HSS cows at the first milking, but no difference between groups was found from the second to sixth milking. Yield of α-LA in milk was lower in HSS than in LSS during the first 6 milkings postpartum, especially in colostrum. Concentrations of α-LA, IgG₁, and IgG₂ in milk did not differ between groups during the entire experiment except for higher IgG observed in LSS than in HSS at the second milking and for higher IgG₂ found in HSS compared with LSS on d 5. In contrast, SA concentrations and LDH activity in milk were lower in LSS compared with HSS cows during the first 6 milkings postpartum, particularly in colostrum. Milk somatic cell count was higher in HSS than in LSS throughout the study. Higher circulating 5-HT concentrations were associated with an increased transfer of the paracellularly transported SA, LDH, and somatic cell count, especially at the first milking, suggesting that 5-HT affects TJ permeability during closure of the blood–milk barrier at the onset of lactation. Furthermore, higher serum 5-HT concentrations were associated with a lower α-LA yield in milk. A consistent relationship with serum 5-HT concentrations was neither observed for the transfer of IgG₂ nor the primarily transcellular transport of IgG₁ during the first milkings after parturition.     

Plant Neurobiology,a Fascinating Perspective in the Field of Research on Plant Secondary Metabolites

In this Editorial, I comment on the exciting and original topic of plant neurobiology, focusing on natural products whose biosynthesis is shared by animal and plant organisms, i.e., indoleamines (melatonin and serotonin) and catecholamines (dopamine, norepinephrine and epinephrine).     

Association of the serotonin transporter gene promoter region (5-HTTLPR) polymorphism with biased attention for emotional stimuli.

A deletion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with vulnerability to affective disorders, yet the mechanism by which this gene confers vulnerability remains unclear. Two studies examined associations between the 5-HTTLPR polymorphism and attentional bias for emotional stimuli among nondepressed adults. Biased attention, attention engagement, and difficulty with attention disengagement were assessed with a spatial cuing task using emotional stimuli. Results from Study 1 (N = 38) indicated that short 5-HTTLPR allele carriers experienced greater difficulty disengaging their attention from sad and happy stimuli compared with long allele homozygotes. Study 2 participants (N = 144) were genotyped for the 5-HTTLPR polymorphism, including single nucleotide polymorphism rs25531 in the long allele of the 5-HTTLPR. Consistent with Study 1, individuals homozygous for the low-expressing 5-HTTLPR alleles (i.e., S and LG) experienced greater difficulty disengaging attention from sad, happy, and fear stimuli than high-expressing 5-HTTLPR homozygotes. Because this association exists in healthy adults, it may represent a susceptibility factor for affective disorders that becomes problematic during stressful life experiences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nonhuman primate neuroimaging and cocaine medication development.

Given the important role of the dopamine transporter (DAT) in the addictive properties of cocaine, the development and use of compounds that target the DAT represents a reasonable approach for the pharmacological treatment of cocaine abuse. The present report describes a series of studies conducted in nonhuman primates that evaluated the effectiveness of DAT inhibitors in reducing cocaine self-administration. In addition, drug substitution studies evaluated the abuse liability of the DAT inhibitors. Positron emission tomography neuroimaging studies quantified DAT occupancy at behaviorally relevant doses, characterized the time-course of drug uptake in brain, and documented drug-induced changes in cerebral blood flow as a model of brain activation. Selective DAT inhibitors were effective in reducing cocaine use but high (>70%) levels of DAT occupancy were associated with significant reductions in cocaine self-administration. The selective DAT inhibitors were reliably self-administered but rates of responding were lower than those maintained by cocaine even at higher levels of DAT occupancy. A profile of slow rate of drug uptake in brain accompanied by a gradual increase in extracellular dopamine may account for the more limited reinforcing effectiveness of the DAT inhibitors. Selective serotonin transporter (SERT) inhibitors were also effective in reducing cocaine use and blocked cocaine-induced brain activation and increases in extracellular dopamine. Coadministration of SERT inhibitors with a selective DAT inhibitor was more effective than the DAT inhibitor administered alone, even at comparable levels of DAT occupancy. The results indicate that combined inhibition of DAT and SERT may be a viable approach to treat cocaine addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)