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Background Cortical dopaminergic systems are critically involved in prefrontal cortex (PFC) functions, especially in working memory and neurodevelopmental disorders such as schizophrenia. GSK-3β (glycogen synthase kinase-3β) is highly associated with cAMP (cyclic adenosine monophosphate)–independent dopamine D2 receptor (D2R)-mediated signaling to affect dopamine-dependent behaviors. However, the mechanisms underlying the GSK-3β modulation of cognitive function via D2Rs remains unclear. Methods This study explored how conditional cell-type–specific ablation of GSK-3β in D2R+ neurons (D2R-GSK-3β−/−) in the brain affects synaptic function in the medial PFC (mPFC). Both male and female (postnatal days 60–90) mice, including 140 D2R, 24 D1R, and 38 DISC1 mice, were used. Results This study found that NMDA receptor (NMDAR) function was significantly increased in layer V pyramidal neurons in mPFC of D2R-GSK-3β−/− mice, along with increased dopamine modulation of NMDAR-mediated current. Consistently, NR2A and NR2B protein levels were elevated in mPFC of D2R-GSK-3β−/− mice. This change was accompanied by a significant increase in enrichment of activator histone mark H3K27ac at the promoters of both Grin2a and Grin2b genes. In addition, altered short- and long-term synaptic plasticity, along with an increased spine density in layer V pyramidal neurons, were detected in D2R-GSK-3β−/− mice. Indeed, D2R-GSK-3β−/− mice also exhibited a resistance of working memory impairment induced by injection of NMDAR antagonist MK-801. Notably, either inhibiting GSK-3β or disrupting the D2R-DISC1 complex was able to reverse the mutant DISC1-induced decrease of NMDAR-mediated currents in the mPFC. Conclusions This study demonstrates that GSK-3β modulates cognition via D2R-DISC1 interaction and epigenetic regulation of NMDAR expression and function.

Primary cerebellar agenesis (PCA), a brain disease where the cerebellum does not develop, is an extremely rare congenital disease with only eleven living cases reported thus far. Studies of the PCA case will thus provide valuable insights into the necessity of cerebellar development for controlling and modulating cognitive functions of the brain. In this follow-up study, we further investigated the performance of associative learning and time perception of a 26-year-old female complete PCA case. We assessed whether delayed eyeblink conditioning (EBC), which represents prototypical associative motor learning function of the cerebellum, could be partially compensated by the extracerebellar brain regions in complete absence of the cerebellum. We also assessed whether the cerebellum, a critical brain region for millisecond-range interval timing, is essential for perception of the second-range time interval. Twelve neurotypical age-matched individuals were used as controls. We found that although the complete PCA patient had only mild to moderate motor deficits, she was unable to perform the delayed EBC even after 1-week of extensive training. Additionally, the PCA patient also performed poorly during time reproduction experiments in which she overproduced the millisecond-range time intervals, while underproduced the second-range time intervals. The PCA patient also failed to perform the temporal eyeblink conditioning with a 5 s fixed interval as the conditioned stimulus. These results indicate that the cerebellum is indispensable for associative motor learning and involved in timing of sub-second intervals, as well as in the perception of second-range intervals.

Prodromal memory deficits represent an important marker for the development of schizophrenia (SZ), in which glutamatergic hypofunction occurs in the prefrontal cortex (PFC). The mGluR2/3 agonist LY379268 (LY37) attenuates excitatory N-methyl-D-aspartate receptor (NMDAR)-induced neurotoxicity, a central pathological characteristic of glutamatergic hypofunction. We therefore hypothesized that early treatment with LY37 would rescue cognitive deficits and confer benefits for SZ-like behaviors in adults. To test this, we assessed whether early intervention with LY37 would improve learning outcomes in the Morris Water Maze for rats prenatally exposed to methylazoxymethanol acetate (MAM), a neurodevelopmental SZ model. We found that a medium dose of LY37 prevents learning deficits in MAM rats. These effects were mediated through postsynaptic mGluR2/3 via improving GluN2B-NMDAR function by inhibiting glycogen synthase kinase-3β (GSK3β). Furthermore, dendritic spine loss and learning and memory deficits observed in adult MAM rats were restored by juvenile LY37 treatment, which did not change prefrontal neuronal excitability and glutamatergic synaptic transmission in adult normal rats. Our results provide a mechanism for mGluR2/3 agonists against NMDAR hypofunction, which may prove to be beneficial in the prophylactic treatment of SZ.

Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder, in which cognitive function becomes disrupted at early stages of the disease. Although the mechanisms underlying cognitive impairments remain unclear, N-methyl-D-aspartate receptors (NMDAR) hypofunctioning in the prefrontal cortex (PFC) has been implicated. Moreover, cognitive symptoms in SCZ are usually unresponsive to treatment with current antipsychotics and by onset, disruption of the dopamine system, not NMDAR hypofunctioning, dominates the symptoms. Therefore, treating cognitive deficits at an early stage is a realistic approach. In this study, we tested whether an early treatment targeting mGluR2 would be effective in ameliorating cognitive impairments in the methylazoxymethanol acetate (MAM) model of SCZ. We investigated the effects of an mGluR2 agonist/mGluR3 antagonist, LY395756 (LY39), on the NMDAR expression and function in juveniles, as well as cognitive deficits in adult rats after juvenile treatment. We found that gestational MAM exposure induced a significant decrease in total protein levels of the NMDAR subunit, NR2B, and a significant increase of pNR2BTyr1472 in the juvenile rat PFC. Treatment with LY39 in juvenile MAM-exposed rats effectively recovered the disrupted NMDAR expression. Furthermore, a subchronic LY39 treatment in juvenile MAM-exposed rats also alleviated the learning deficits and cognitive flexibility impairments when tested with a cross-maze based set-shifting task in adults. Therefore, our study demonstrates that targeting dysfunctional NMDARs with an mGluR2 agonist during the early stage of SCZ could be an effective strategy in preventing the development and progression in addition to ameliorating cognitive impairments of SCZ.

Ephedrae Herba (EH, Ephedra sinica Stapf.) and Armeniacae Semen Amarum (ASA, Prunus armeniaca L. var. ansu Maxim.) have been used to treat asthma, cold, fever, and cough in China for thousands of years.In this study, we aimed to investigate the optimal ratio of EH and ASA compatibility (EAC) to reduce airway injury in asthmatic rats and its possible mechanism.Rats were sensitized with a mixture of acetylcholine chloride and histamine bisphosphate 1 h before sensitization by intragastric administration of EAC or dexamethasone or saline for 7 days. Subsequently, the ultrastructure of rat airway epithelial tissue changes, apoptosis of the airway epithelial cells, and the expression of mRNA and protein of EGRF and Bcl-2 were detected.Transmission electron microscope: EAC (groups C and E) had the most prominent effect on repairing airway epithelial cells' ultrastructural changes in asthmatic rats. TUNEL: dexamethasone and EAC (groups B、C、E and F) inhibited the apoptosis of airway epithelial cells in asthmatic rats (P 0.05). In situ hybridization: EAC (group E) inhibited the overexpression of EGFR and Bcl-2 mRNA (P 0.05).Western Blotting: EAC (groups A、B、C、E and F) inhibited the upregulation of airway epithelial EGFR and Bcl-2 protein expression (P 0.01).Our findings indicate that EAC can inhibit abnormal changes in airway epithelial structure and apoptosis of airway epithelial cells, thereby alleviating airway injury. In this study, the best combination of EH and ASA to alleviate airway epithelial injury in asthmatic rats was group E (EH: ASA = 8: 4.5).

Among the neuromodulators that regulate prefrontal cortical circuit function, the catecholamine transmitters norepinephrine (NE) and dopamine (DA) stand out as powerful players in working memory and attention. Perturbation of either NE or DA signaling is implicated in the pathogenesis of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia, and drug addiction. Although the precise mechanisms employed by NE and DA to cooperatively control prefrontal functions are not fully understood, emerging research indicates that both transmitters regulate electrical and biochemical aspects of neuronal function by modulating convergent ionic and synaptic signaling in the prefrontal cortex (PFC). This review summarizes previous studies that investigated the effects of both NE and DA on excitatory and inhibitory transmissions in the prefrontal cortical circuitry. Specifically, we focus on the functional interaction between NE and DA in prefrontal cortical local circuitry, synaptic integration, signaling pathways, and receptor properties. Although it is clear that both NE and DA innervate the PFC extensively and modulate synaptic function by activating distinctly different receptor subtypes and signaling pathways, it remains unclear how these two systems coordinate their actions to optimize PFC function for appropriate behavior. Throughout this review, we provide perspectives and highlight several critical topics for future studies. This article is part of a Special Issue entitled SI: Noradrenergic System.

Postsynaptic Density Protein-95 (PSD-95) is a major scaffolding protein in the excitatory synapses in the brain and a critical regulator of synaptic maturation for NMDA and AMPA receptors. PSD-95 deficiency has been linked to cognitive and learning deficits implicated in neurodevelopmental disorders such as autism and schizophrenia. Previous studies have shown that PSD-95 deficiency causes a significant reduction in the excitatory response in the hippocampus. However, little is known about whether PSD-95 deficiency will affect gamma-aminobutyric acid (GABA)ergic inhibitory synapses. Using a PSD-95 transgenic mouse model (PSD-95+/−), we studied how PSD-95 deficiency affects GABAA receptor expression and function in the medial prefrontal cortex (mPFC) during adolescence. Our results showed a significant increase in the GABAA receptor subunit α1. Correspondingly, there are increases in the frequency and amplitude in spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons in the mPFC of PSD-95+/− mice, along with a significant increase in evoked IPSCs, leading to a dramatic shift in the excitatory-to-inhibitory balance in PSD-95 deficient mice. Furthermore, PSD-95 deficiency promotes inhibitory synapse function via upregulation and trafficking of NLGN2 and reduced GSK3β activity through tyr-216 phosphorylation. Our study provides novel insights on the effects of GABAergic transmission in the mPFC due to PSD-95 deficiency and its potential link with cognitive and learning deficits associated with neuropsychiatric disorders.

Glycogen synthase kinase 3β (GSK3β) has gained interest regarding its involvement in psychiatric and neurodegenerative disorders. Recently GSK3 inhibitors were highlighted as promising rescuers of cognitive impairments for a gamut of CNS disorders. Growing evidence supports that fast-spiking parvalbumin (PV) interneurons are critical regulators of cortical computation. Albeit, how excitatory receptors on PV interneurons are regulated and how this affects cognitive function remains unknown. To address these questions, we have generated a novel triple-transgenic conditional mouse with GSK3β genetically deleted from PV interneurons. PV-GSK3β-/- resulted in increased excitability and augmented excitatory synaptic strength in prefrontal PV interneurons. More importantly, these synaptic changes are correlated with accelerated learning with no changes in locomotion and sociability. Our study, for the first time, examined how GSK3β activity affects learning capability via regulation of PV interneurons. This study provides a novel insight into how GSK3β may contribute to disorders afflicted by cognitive deficits.

Targeting group II metabotropic glutamate receptors (mGluR2/3) has been proposed to correct the dysfunctional glutamatergic system, particularly NMDA receptor (NMDAR) hypofunction, for treatment of schizophrenia. However, how activation of mGluR2/3 affects NMDAR function in adult animals remains elusive. Here we show the effects of LY395756 (LY39), a compound acting as both an mGluR2 agonist and mGluR3 antagonist, on the NMDAR expression and function of normal adult rat prefrontal cortex (PFC) as well as working memory function in the MK801 model of schizophrenia. We found that in vivo administration of LY39 significantly increased the total protein levels of NMDAR subunits and NR2B phosphorylationin the PFC, along with the amplitude of NMDAR-mediated miniature excitatory postsynaptic currents (mEPSC) in the prefrontal cortical neurons. Moreover, LY39 also significantly increased mTOR and pmTOR expression, but not ERK1/2, Akt, and GSK3β, suggesting an activation of mTOR signaling. Indeed, the mTOR inhibitor rapamycin, and actinomycin-D, a transcription inhibitor, blocked the enhanced effects of LY39 on NMDAR-mEPSCs. These results indicate that LY39 regulates NMDAR expression and function through unidentified mTOR-mediated protein synthesis in the normal adult rat PFC. However, this change is insufficient to affect working memory function in normal animals, nor to reverse the MK801-induced working memory deficit. Our data provide the first evidence of an in vivo effect of a novel compound that acts as both an mGluR2 agonist and mGluR3 antagonist on synaptic NMDAR expression and function in the adult rat PFC, although its effect -on PFC-dependent cognitive function remains to be explored.

The prefrontal cortex (PFC) is a brain region featured with working memory function. The exact mechanism of how working memory operates within the PFC circuitry is unknown, but persistent neuronal firing recorded from prefrontal neurons during a working memory task is proposed to be the neural correlate of this mnemonic encoding. The PFC appears to be specialized for sustaining persistent firing, with N-methyl-D-aspartate (NMDA) receptors, especially slow-decay NR2B subunits, playing an essential role in the maintenance of sustained activity and normal working memory function. However, the NR2B subunit serves as a double-edged sword for PFC function. Because of its slow kinetics, NR2B endows the PFC with not only “neural psychic” properties, but also susceptibilities for neuroexcitotoxicity and psychiatric disorders. This review aims to clarify the interplay among working memory, the PFC, and NMDA receptors; demonstrate the importance of the NR2B subunit in the maintenance of persistent activity; understand the risks and vulnerabilities of how NR2B is related to the development of neuropsychiatric disorders; identify gaps that currently exist in our understanding of these processes; and provide insights regarding future directions that may clarify these issues. We conclude that the PFC is a specialized brain region with distinct delayed maturation, unique neuronal circuitry, and characteristic NMDA receptor function. The unique properties and development of NMDA receptors, especially enrichment of NR2B subunits, endows the PFC with not only the capability to generate sustained activity for working memory, but also serves as a major vulnerability to environmental insults and risk factors for psychiatric disorders.

Group II metabotropic glutamate receptor (mGluR2/3) agonists once showed promise as non-dopaminergic antipsychotic drugs because of their efficacy in alleviating symptoms of schizophrenia (SZ) in both animal models and human patients. However, the recent failure of Phase III clinical trials dealt a huge blow to the scientific community and the aftershock of the setback in mGluR2/3 research can be felt everywhere from grant support and laboratory studies to paper publication. An immediate question raised is whether mGluR2/3 is still a promising therapeutic target for schizophrenia. Answering this question is not easy, but apparently a new strategy is needed. This article provides a focused review of literature on the study of mGluR2/3 agonists, especially on mGluR2/3 agonists' mechanism of action and efficacy in both normal conditions and animal models of SZ, as well as clinical studies in human patients with the disease. We argue that the cellular and molecular actions of mGluR2/3 agonists, the distinct roles between mGluR2 and mGluR3, as well as their effects on different stages of the disease and different subpopulations of patients, remain incompletely studied. Until the mechanisms associated with mGluR2/3 are clearly elucidated and all treatment options are tested, it would be a great mistake to terminate the study of mGluR2/3 as a therapeutic target for schizophrenia. This review will thus shed light on the comprehensive features of the translational potential mGluR2/3 agonists as well as the need for further research into the more selective activation of mGluR2.

Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug for juveniles and adolescents. Used to treat attention-deficit/hyperactivity disorder (ADHD) and for cognitive enhancement in healthy individuals, it has been regarded as a relatively safe medication for the past several decades. However, a thorough review of the literature reveals that the age-dependent activities of the drug, as well as potential developmental effects, are largely ignored. In addition, the diagnosis of ADHD is subjective, leaving open the possibility of misdiagnosis and excessive prescription of the drug. Recent studies have suggested that early life exposure of healthy rodent models to methylphenidate resulted in altered sleep/ wake cycle, heightened stress reactivity, and, in fact, a dosage previously thought of as therapeutic depressed neuronal function in juvenile rats. Furthermore, juvenile rats exposed to low-dose methylphenidate displayed alterations in neural markers of plasticity, indicating that the drug might alter the basic properties of prefrontal cortical circuits. In this review of the current literature, we propose that juvenile exposure to methylphenidate may cause abnormal prefrontal function and impaired plasticity in the healthy brain, strengthening the case for developing a more thorough understanding of methylphenidate’s actions on the developing, juvenile brain, as well as better diagnostic measures for ADHD.

Methylphenidate (Ritalin, MPH) is the most commonly prescribed psychoactive drug for children. Used to treat attention-deficit/hyperactivity disorder (ADHD) and for cognitive enhancement in healthy individuals, its cellular mechanisms of action and potential long-term effects are poorly understood. We recently reported that a clinically relevant (1 mg/kg i.p., single injection) dose of MPH significantly decreased neuronal excitability in the juvenile rat prefrontal cortical neurons. Here we further explore the actions of acute treatment with MPH on the level of NMDA receptor subunits and NMDA receptor-mediated short- and long-term synaptic plasticity in the juvenile rat prefrontal cortical neurons. We found that a single dose of MPH treatment (1 mg/kg, intraperitoneal) significantly decreased the surface and total protein levels of NMDA receptor subunits NR1 and NR2B, but not NR2A, in the juvenile prefrontal cortex. In addition, the amplitude, decay time and charge transfer of NMDA receptor-mediated EPSCs were significantly decreased whereas the amplitude and short-term depression of AMPA receptor-mediated EPSCs were significantly increased in the prefrontal neurons. Furthermore, MPH treatment also significantly increased the probability and magnitude of LTP induction, but had only a small effect on LTD induction in juvenile rat prefrontal cortical neurons. Our data thus present a novel mechanism of action of MPH, i.e., changes in glutamatergic receptor-mediated synaptic plasticity following early-life treatment. Furthermore, since a single dosage resulted in significant changes in NMDA receptors, off-label usage by healthy individuals, especially children and adolescents, may result in altered potential for plastic learning.

Four 2-yr old alpacas ((48±2.3) kg) and four 2-yr old sheep ((50±1.7) kg) were used to study the pH and microbial community of forestomach from alpacas (Lama pacos) and sheep (Ovis aries) fed fresh alfalfa as the sole forage at low altitude (793 m). The forestomach fluid was taken anaerobically via the esophagus. The electric pH meter and quantitative polymerase chain reaction systems were used to study the the pH and microbial community of forestomach. The results showed that the mean pH of forestomach fluid from alpacas was higher than that from sheep (P

N-methyl-d-aspartic acid (NMDA) receptors are critical for both normal brain functions and the pathogenesis of schizophrenia. We investigated the functional changes of glutamatergic receptors in the pyramidal cells and fast-spiking (FS) interneurons in the adolescent rat prefrontal cortex in MK-801 model of schizophrenia. We found that although both pyramidal cells and FS interneurons were affected by in vivo subchronic blockade of NMDA receptors, MK-801 induced distinct changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors in the FS interneurons compared with pyramidal cells. Specifically, the amplitude, but not the frequency, of AMPA-mediated miniature excitatory postsynaptic currents (mEPSCs) in FS interneurons was significantly decreased whereas both the frequency and amplitude in pyramidal neurons were increased. In addition, MK-801-induced new presynaptic NMDA receptors were detected in the glutamatergic terminals targeting pyramidal neurons but not FS interneurons. MK-801 also induced distinct alterations in FS interneurons but not in pyramidal neurons, including significantly decreased rectification index and increased calcium permeability. These data suggest a distinct cell-type specific and homeostatic synaptic scaling and redistribution of AMPA and NMDA receptors in response to the subchronic blockade of NMDA receptors and thus provide a direct mechanistic explanation for the NMDA hypofunction hypothesis that have long been proposed for the schizophrenia pathophysiology.

Two bacterial 16S rRNA gene clone libraries were constructed from the forestomach of alpacas and sheep fed alfalfa. After the amplification using the universal 16S rRNA gene primers, equal quantities of PCR products from the same species were mixed and used to construct the two libraries. Sequence analysis showed that the 60 clones from alpacas were divided into 27 phylotypes with 25% clones affiliated with Eubacterium sp. F1. The 60 clones from sheep were divided into 21 phylotypes with 7 phylotypes affiliated with Prevotella ruminicola (40% clones). Clones closely related to Clostridium proteoclasticum, Eubacterium sp. F1, Clostridium cellobioparum, Mogibacterium neglectum, Eubacterium ventriosum, Clostridiaceae bacterium WN011, Clostridium coccoides, Clostridium orbiscindens, Eubacterium sp. F1, Cytophaga sp. Dex80-37, Treponema bryantii and Pelotomaculum sp. FP were only found in the forestomach of alpacas, and those to Anaerovorax odorimutans, Treponema zioleckii, Bifidobacterium indicum, Paludibacter propionicigenes, Paraprevotella clara, Eubacterium siraeum, Desulfotomaculum sp. CYP1, Clostridium bolteae, Clostridium termitidis and Clostridiaceae bacterium DJF_LS40 only in the rumen of sheep. Quantitative real-time PCR revealed that the forestomach of alpacas had significantly lower density of bacteria, with bacterial 16S rRNA gene copies (6.89 [Log10 (copies per gram of wet weight)]), than that of sheep (7.71, P

In this paper we consider the single machine scheduling problems with time-dependent deterioration and exponential learning effect, i.e., the actual processing time of a job depends not only on the processing times of the jobs already processed but also on its scheduled position. We consider the following objective functions: the makespan, the sum of the @dth (@d>=0) power of job completion times, the total weighted completion time and the maximum lateness. We show that the makespan minimization problem, the sum of the @dth power of job completion times minimization problem can be solved by the smallest (normal) processing time first (SPT) rule, respectively. We also show that the total weighted completion time minimization problem and the maximum lateness minimization problem can be solved in polynomial time under certain conditions.

The objective was to evaluate effects of feeding sorghum-sudan- or alfalfa-based diets on intake, first compartment stomach characteristics, digestibility, nitrogen balance and energy metabolism in alpacas at low altitude (793 m). Six mature alpacas (42 ± 2.3 kg of body weight) were used in a replicated 3 × 3 Latin square experiment. The treatments were: sorghum-sudan diets (SSD), alfalfa hay diets (AHD) and fresh alfalfa diets (FAD), respectively. Alpacas were housed in metabolism crates and diets were fed for 21 days with 11 d of adaptation and 10 d of sampling. Alpaca was supplemented concentrate with 160 g per alpaca per day and forages were fed at 12 h intervals with water provided ad libitum. First compartment stomach pH and ammonia N were unaffected by forage source, whereas total VFA concentration was different between diets, with the least for FAD (46.8 mM), followed by AHD (51.8 mM) and the highest for SSD (56.1 mM). Ratio of acetate to propionate was greater for AHD and SSD than for FAD diets. The molar proportion of acetate decreased, whereas the molar proportion of propionate increased for FAD relative to AHD and SSD. Redox potential was lower for SSD than for FAD. Surface tension was greater for FAD than for SSD and AHD. Osmolality was lower for FAD than for SSD and AHD. First compartment pressure and methane production tended to be higher for FAD than for SSD (P

The objective was to investigate the forestomach fermentation characteristics and diet digestibility in alpacas ( Lama pacos ) and sheep ( Ovis aries ) fed sorghum-sudan or alfalfa at low altitude (793 m). Four 2-year-old alpacas (48 ± 2.3 kg) and four 2-year-old sheep (50 ± 1.7 kg) were used in a study designed as split-plot in two replicated 2 × 2 Latin square, respectively, for alpacas and sheep. The main plot was species (alpacas and sheep) and the subplot was forage source (sorghum-sudan and alfalfa). Diet consisted of 700 g kg −1 forage, which was either sorghum-sudan or alfalfa, and 300 g kg −1 corn-based concentrate (dry matter [DM] basis). The animals were housed in metabolism crates and were fed twice daily for 21 days of each experimental period, with 11 days of adaptation and 10 days of sampling. There was interaction between species and forage on total volatile fatty acid (VFA) concentrations. The concentrations of total VFA decreased by substitution of sorghum-sudan with alfalfa in both species, but the magnitude of the reduction was smaller in alpacas (−17%) than in sheep (−34%). The molar proportions of acetate and BCFA were higher, whereas those of butyrate were lower in alpacas than in sheep with similar proportion of propionate as well as ratio of acetate to propionate between alpacas and sheep. Replacing sorghum-sudan with alfalfa in the diet reduced the ratio of acetate to propionate due to the reduced proportion of acetate and increased proportion of propionate. Ammonia N concentration was about 28% lower in alpacas than in sheep, with no difference between the forages. Redox potential, forestomach pressure, osmolality and methane production were overall lower in alpacas than in sheep. There were no interactions of species with forage source on digestibilities in the total tract. The species had minimal effect on the total digestibilities of nutrients but digestibilities of fibre were lower with alfalfa than with sorghum-sudan diet. The results revealed not only the great differences in forestomach fermentation, but also the similarity of digestibility of nutrients in the total tract between alpacas and sheep at low altitude (793 m).