Scalable Production of Equine Platelet Lysate for Multipotent Mesenchymal Stromal Cell Culture.

Translation of multipotent mesenchymal stromal cell (MSC)-based therapies is advancing in human and veterinary medicine. One critical issue is the in vitro culture of MSC before clinical use. Using fetal bovine serum (FBS) as supplement to the basal medium is still the gold standard for cultivation of many cell types including equine MSC. Alternatives are being explored, with substantial success using platelet lysate-supplemented media for human MSC. However, progress lags behind in the veterinary field. The aim of this study was to establish a scalable protocol for equine platelet lysate (ePL) production and to test the ePL in equine MSC culture. Whole blood was harvested into blood collection bags from 20 healthy horses. After checking sample materials for pathogen contamination, samples from 19 animals were included. Platelet concentrates were prepared using a buffy coat method. Platelets, platelet-derived growth factor BB, and transforming growth factor ß1 concentrations were increased in the concentrates compared with whole blood or serum (p < 0.05), while white blood cells were reduced (p < 0.05). The concentrates were lysed using freeze/thaw cycles, which eliminated the cells while growth factor concentrations were maintained. Donor age negatively correlated with platelet and growth factor concentrations after processing (p < 0.05). Finally, all lysates were pooled and the ePL was evaluated as culture medium supplement in comparison with FBS, using adipose-derived MSC from four unrelated donor horses. MSC proliferated well in 10% FBS as well as in 10% ePL. However, using 5 or 2.5% ePL entailed highly inconsistent proliferation or loss of proliferation, with significant differences in generation times and confluencies (p < 0.05). MSC expressed the surface antigens CD90, CD44, and CD29, but CD73 and CD105 detection was low in all culture media. Adipogenic and osteogenic differentiation led to similar results in MSC from different culture media. The buffy coat method is useful to produce equine platelet concentrate with increased platelet and reduced white blood cell content in large scales. The ePL obtained supports MSC expansion similar as FBS when used at the same concentration (10%). Further investigations into equine MSC functionality in culture with ePL should follow.

Comparison between adult and foetal adnexa derived equine post-natal mesenchymal stem cells.

BACKGROUND: Little is known about the differences among adult and foetal equine mesenchymal stem cells (MSCs), and no data exist about their comparative ultrastructural morphology. The aim of this study was to describe and compare characteristics, immune properties, and ultrastructural morphology of equine adult (bone marrow: BM, and adipose tissue: AT) and foetal adnexa derived (umbilical cord blood: UCB, and Wharton's jelly: WJ) MSCs. RESULTS: No differences were observed in proliferation during the first 3 passages. While migration ability was similar among cells, foetal MSCs showed a higher adhesion ability, forming smaller spheroids after hanging drop culture (P < 0.05). All MSCs differentiated toward adipogenic, chondrogenic and osteogenic lineages, only tenogenic differentiation was less evident for WJ-MSCs. Data obtained by PCR confirmed MHC1 expression and lack of MHC2 expression in all four cell types. Foetal adnexa MSCs were positive for genes specific for anti-inflammatory and angiogenic factors (IL6, IL8, ILß1) and WJ-MSCs were the only positive for OCT4 pluripotency gene. At immunofluorescence all cells expressed typical mesenchymal markers (α-SMA, N-cadherin), except for BM-MSCs, which did not express N-cadherin. By transmission electron microscopy, it was observed that WJ-MSCs had a higher (P < 0.05) number of microvesicles compared to adult MSCs, and UCB-MSCs showed more microvesicles than BM-MSCs (P < 0.05). AT-MSCs had a lower number of mitochondria than WJ-MSCs (P < 0.05), and mitochondrial area was higher for WJ-MSCs compared to UCB and AT-MSCs (P < 0.05). CONCLUSIONS: Results demonstrate that MSCs from adult and foetal tissues have different characteristics, and foetal MSCs, particularly WJ derived ones, seem to have some charactestics that warrant further investigation into potential advantages for clinical application.

'Say no': a feasibility trial of a brief intervention to reduce instances of indulgent energy-intake episodes.

The aim of this study is to examine the feasibility of a brief intervention to reduce instances of indulgent energy intake. Forty-five participants with a body mass index (BMI) ≥25 kg m-2 were randomized to one of three groups for 8 weeks. The control group was asked to complete a questionnaire every 4 days, the self-monitoring group was given the same instructions but also asked to 'say no' to indulgences. The self-monitoring and feedback group was asked to do the same but in addition to send a photograph or description of that to which they had 'said no' and were then provided with feedback. All participants reported on indulgences for 7 days prospectively at baseline and 8-week follow-up. The follow-up rate was 80%; completion of questionnaires was 63% and 87 text messages were sent. The control group reduced their indulgences by 4.1 (SD 10.0), the self-monitoring group by 13.8 (SD 16.8) and self-monitoring and feedback group by 9.0 (SD 11.7) per week. All bar one, feasibility progression criteria were met and this was the return of the indulgence diaries during the intervention period. The study demonstrates the feasibility of a brief intervention to reduce the number of indulgences people ate. The progression criteria were met and areas of improvement are highlighted.

Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model.

BACKGROUND: Mesenchymal stromal cells (MSC) have shown promising results in the treatment of tendinopathy in equine medicine, making this therapeutic approach seem favorable for translation to human medicine. Having demonstrated that MSC engraft within the tendon lesions after local injection in an equine model, we hypothesized that they would improve tendon healing superior to serum injection alone. METHODS: Quadrilateral tendon lesions were induced in six horses by mechanical tissue disruption combined with collagenase application 3 weeks before treatment. Adipose-derived MSC suspended in serum or serum alone were then injected intralesionally. Clinical examinations, ultrasound and magnetic resonance imaging were performed over 24 weeks. Tendon biopsies for histological assessment were taken from the hindlimbs 3 weeks after treatment. Horses were sacrificed after 24 weeks and forelimb tendons were subjected to macroscopic and histological examination as well as analysis of musculoskeletal marker expression. RESULTS: Tendons injected with MSC showed a transient increase in inflammation and lesion size, as indicated by clinical and imaging parameters between week 3 and 6 (p < 0.05). Thereafter, symptoms decreased in both groups and, except that in MSC-treated tendons, mean lesion signal intensity as seen in T2w magnetic resonance imaging and cellularity as seen in the histology (p < 0.05) were lower, no major differences could be found at week 24. CONCLUSIONS: These data suggest that MSC have influenced the inflammatory reaction in a way not described in tendinopathy studies before. However, at the endpoint of the current study, 24 weeks after treatment, no distinct improvement was observed in MSC-treated tendons compared to the serum-injected controls. Future studies are necessary to elucidate whether and under which conditions MSC are beneficial for tendon healing before translation into human medicine.

Characterisation and intracellular labelling of mesenchymal stromal cells derived from synovial fluid of horses and sheep.

Multipotent mesenchymal stromal cells (MSCs) derived from synovial fluid (SF) are considered to be a promising cell type for therapeutic applications in joint disease. However, despite their potential relevance for clinical and experimental studies, there is insufficient knowledge about SF-derived MSCs isolated from horses and sheep. In this study, cells were recovered from healthy SF and bone marrow (BM) of sheep, and from healthy and osteoarthritic SF of horses. Ovine SF-MSCs were used to assess the efficiency of intracellular labelling with quantum dots (QDs). Colony forming units, generation times, trilineage differentiation potential and expression of CD73, CD90 and CD105 at mRNA level were assessed. QD labelling was efficient, with >98% positive cells directly after labelling at 10 nmol/L and >95% positive cells directly after labelling at 2 nmol/L. The label decreased over 7 days of culture, with more persistence at the higher labelling concentration. No significant differences in proliferation were observed. All MSCs had trilineage differentiation potential, but adipogenesis was more distinct in equine samples and chondrogenesis was most pronounced in ovine SF-MSCs. CD73, CD90 and CD105 were expressed in equine and ovine MSCs.

Parametrization of nanoparticles: development of full-particle nanodescriptors.

While metal oxide nanoparticles (NPs) are one of the most commonly used nanomaterials, the theoretical models used to analyze and predict their behavior have been mostly based on just the chemical composition or the extrapolation from small metal oxide clusters' calculations. In this study, a set of novel, theoretical full-particle descriptors for modeling, grouping or read-across of metal oxide NP properties and biological activity was developed based on the force-field calculation of the potential energies of whole NPs. The capability of these nanodescriptors to group the nanomaterials acoording to their biological activity was demonstrated by Principal Component Analysis (PCA). The grouping provided by the PCA approach was found to be in good accordance with the algal growth inhibition data of well characterized nanoparticles, synthesized and measured inside the consortia of the EU 7FP framework MODERN project.

[MR defaecography for the diagnosis of obstructive defaecation disorders]. / MR-Defäkografie bei obstruktiven Defäkationsstörungen.

As a consequence of demographic changes, outlet obstruction represents an increasingly common disease. The presence and ample interactions of morphological and functional pathologies contribute to the complexity of pelvic floor dysfunction. Additionally, multiple compartments of the pelvic floor are frequently affected. MR defaecography allows for the simultaneous and detailed assessment of morphological as well as functional changes of the pelvic floor. Hence, this approach constitutes an integral part of the diagnostic work-up and preoperative evaluation of the anorectum. The supine patient position can be regarded as a drawback compared to conventional defaecography, as sufficient emptying of the rectum can be impaired or even rendered impossible in individual cases. This inherent disadvantage is, however, compensated by the high anatomic resolution, the possibility of multiplanar imaging, easy execution and especially the lack of ionising radiation. Consequently, MR defaecography is considered the method of choice for the routine evaluation of functional anorectal disorders.

Epithelioid angiosarcoma of the scapula.

Epithelioid angiosarcoma is a rare variation of an angiosarcoma and its localization in the bone is exceptionally infrequent. This report presents the case of a 48-year-old male with an epithelioid angiosarcoma of the scapula. In CT and MRI scans an inhomogeneous tumour with osseous destructions, lytic areas, central necrosis and marginal hyperperfusion was observed. The bordering skeletal muscles were already infiltrated. The tumour was treated initially with neoadjuvant chemotherapy, followed by dose escalation, peripheral blood stem cell transplantation and resection of the lesion. Despite advanced local tumour stage at initial presentation, the patient is in complete remission.

Basic science and clinical application of stem cells in veterinary medicine.

Stem cells play an important role in veterinary medicine in different ways. Currently several stem cell therapies for animal patients are being developed and some, like the treatment of equine tendinopathies with mesenchymal stem cells (MSCs), have already successfully entered the market. Moreover, animal models are widely used to study the properties and potential of stem cells for possible future applications in human medicine. Therefore, in the young and emerging field of stem cell research, human and veterinary medicine are intrinsically tied to one another. Many of the pioneering innovations in the field of stem cell research are achieved by cooperating teams of human and veterinary medical scientists.Embryonic stem (ES) cell research, for instance, is mainly performed in animals. Key feature of ES cells is their potential to contribute to any tissue type of the body (Reed and Johnson, J Cell Physiol 215:329-336, 2008). ES cells are capable of self-renewal and thus have the inherent potential for exceptionally prolonged culture (up to 1-2 years). So far, ES cells have been recovered and maintained from non-human primate, mouse (Fortier, Vet Surg 34:415-423, 2005) and horse blastocysts (Guest and Allen, Stem Cells Dev 16:789-796, 2007). In addition, bovine ES cells have been grown in primary culture and there are several reports of ES cells derived from mink, rat, rabbit, chicken and pigs (Fortier, Vet Surg 34:415-423, 2005). However, clinical applications of ES cells are not possible yet, due to their in vivo teratogenic degeneration. The potential to form a teratoma consisting of tissues from all three germ lines even serves as a definitive in vivo test for ES cells.Stem cells obtained from any postnatal organism are defined as adult stem cells. Adult haematopoietic and MSCs, which can easily be recovered from extra embryonic or adult tissues, possess a more limited plasticity than their embryonic counterparts (Reed and Johnson, J Cell Physiol 215:329-336, 2008). It is believed that these stem cells serve as cell source to maintain tissue and organ mass during normal cell turnover in adult individuals. Therefore, the focus of attention in veterinary science is currently drawn to adult stem cells and their potential in regenerative medicine. Also experience gained from the treatment of animal patients provides valuable information for human medicine and serves as precursor to future stem cell use in human medicine.Compared to human medicine, haematopoietic stem cells only play a minor role in veterinary medicine because medical conditions requiring myeloablative chemotherapy followed by haematopoietic stem cell induced recovery of the immune system are relatively rare and usually not being treated for monetary as well as animal welfare reasons.In contrast, regenerative medicine utilising MSCs for the treatment of acute injuries as well as chronic disorders is gradually turning into clinical routine. Therefore, MSCs from either extra embryonic or adult tissues are in the focus of attention in veterinary medicine and research. Hence the purpose of this chapter is to offer an overview on basic science and clinical application of MSCs in veterinary medicine.

Orexin/hypocretin modulation of the basal forebrain cholinergic system: Role in attention.

The basal forebrain cholinergic system (BFCS) plays a role in several aspects of attentional function. Activation of this system by different afferent inputs is likely to influence how attentional resources are allocated. While it has been recognized for some time that the hypothalamus is a significant source of projections to the basal forebrain, the phenotype(s) of these inputs and the conditions under which their regulation of the BFCS becomes functionally relevant are still unclear. The cell bodies of neurons expressing orexin/hypocretin neuropeptides are restricted to the lateral hypothalamus and contiguous perifornical area but have widespread projections, including to the basal forebrain. Orexin fibers and both orexin receptor subtypes are distributed in cholinergic parts of the basal forebrain, where application of orexin peptides increases cell activity and cortical acetylcholine release. Furthermore, disruption of orexin signaling in the basal forebrain impairs the cholinergic response to an appetitive stimulus. In this review, we propose that orexin inputs to the BFCS form an anatomical substrate for links between arousal and attention, and that these interactions might be particularly important as a means by which interoceptive cues bias allocation of attentional resources toward related exteroceptive stimuli. Dysfunction in orexin-acetylcholine interactions may play a role in the arousal and attentional deficits that accompany neurodegenerative conditions as diverse as drug addiction and age-related cognitive decline.

EOG and EMG: two important switches in automatic sleep stage classification.

Sleep is a natural periodic state of rest for the body, in which the eyes are usually closed and consciousness is completely or partially lost. In this investigation we used the EOG and EMG signals acquired from 10 patients undergoing overnight polysomnography with their sleep stages determined by expert sleep specialists based on RK rules. Differentiation between Stage 1, Awake and REM stages challenged a well trained neural network classifier to distinguish between classes when only EEG-derived signal features were used. To meet this challenge and improve the classification rate, extra features extracted from EOG and EMG signals were fed to the classifier. In this study, two simple feature extraction algorithms were applied to EOG and EMG signals. The statistics of the results were calculated and displayed in an easy to visualize fashion to observe tendencies for each sleep stage. Inclusion of these features show a great promise to improve the classification rate towards the target rate of 100%

Itakura Distance: A Useful Similarity Measure between EEG and EOG Signals in Computer-aided Classification of Sleep Stages.

Sleep is a natural periodic state of rest for the body, in which the eyes usually close and consciousness is completely or partially lost. Consequently, there is a decrease in bodily movements and responsiveness to external stimuli. Slow wave sleep is of immense interest as it is the most restorative sleep stage during which the body recovers from weariness. During this sleep stage, electroencephalographic (EEG) and electro-oculographic (EOG) signals interfere with each other and they share a temporal similarity. In this investigation we used the EEG and EOG signals acquired from 10 patients undergoing overnight polysomnography with their sleep stages determined by certified sleep specialists based on RK rules. In this pilot study, we performed spectral estimation of EEG signals by Autoregressive (AR) modeling, and then used Itakura Distance to measure the degree of similarity between EEG and EOG signals. We finally calculated the statistics of the results and displayed them in an easy to visualize fashion to observe tendencies for each sleep stage. We found that Itakura Distance is the smallest for sleep stages 3 and 4. We intend to deploy this feature as an important element in automatic classification of sleep stages.

The use of R-wave morphology in the detection of sleep-disordered breathing using the electrocardiogram--a comparison between leads.

Power spectral analysis of time series derived from the R-wave morphology of the ECG was employed to identify a suitable lead configuration for the detection of sleep-disordered breathing (SDB) using the electrocardiogram (ECG). 16 subjects (46 +/- 9.2 yrs, 8 males), who did not report problems during sleep, and 13 subjects previously diagnosed with SDB (49 +/- 8.8 yrs, 7 males) underwent an overnight sleep study at an accredited sleep center. Power values derived from the spectra of the R-peaks envelope were tested for their sensitivity and specificity in discriminating between epochs containing normal breathing from epochs containing SDB. Of the three tested lead configurations using two parameters NB1 and NB2 derived from the power spectrum, lead I produced the best results with a sensitivity of 92.8% and a specificity of 88.0% for the case of parameter NB1 and a sensitivity of 85.7% and a specificity of 76.0% for the case of parameter NB2.

EEG feature extraction for classification of sleep stages.

Automated sleep staging based on EEG signal analysis provides an important quantitative tool to assist neurologists and sleep specialists in the diagnosis and monitoring of sleep disorders as well as evaluation of treatment efficacy. A complete visual inspection of the EEG recordings acquired during nocturnal polysomnography is time consuming, expensive, and often subjective. Therefore, feature extraction is implemented as an essential preprocessing step to achieve significant data reduction and to determine informative measures for automatic sleep staging. However, the analysis of the EEG signal and extraction of sensitive measures from it has been a challenging task due to the complexity and variability of this signal. We present three different schemes to extract features from the EEG signal: relative spectral band energy, harmonic parameters, and Itakura distance. Spectral estimation is performed by using autoregressive (AR) modeling. We then compare the performance of these schemes with the view to select an optimal set of features for specific, sensitive, and accurate neuro-fuzzy classification of sleep stages.

Differential cortical acetylcholine release in rats performing a sustained attention task versus behavioral control tasks that do not explicitly tax attention.

The present study used microdialysis techniques to compare acetylcholine release in the frontoparietal cortex of rats performing in a task requiring sustained attention with that of rats performing in two control procedures. The two control procedures were a fixed-interval 9-s schedule of reinforcement assessing primarily the effects of operant responding and comparable reward rates, and an operant procedure designed to test the effects of lever extension to prompt responding. These two control procedures involved comparable sensory-motor and motivational variables to those of the sustained attention task, but did not explicitly tax attentional processes. Performance of the sustained attention task was associated with a significant increase in cortical acetylcholine efflux, reaching a maximum of nearly 140%. Performance of the two control procedures was associated with significantly smaller (approximately 50%) increases in cortical acetylcholine release. This robust dissociation between attentional and control performance-associated increases in cortical acetylcholine release resulted, in part, from the elimination of the pre-task transfer of the animals into the operant chambers and the associated increases in acetylcholine release observed in previous studies. The present results support the hypothesis that demands on attentional performance, as opposed to the frequency of lever pressing, reward delivery and other task-related variables, selectively activate the basal forebrain corticopetal cholinergic system.

Dissociation between the attentional functions mediated via basal forebrain cholinergic and GABAergic neurons.

The role of basal forebrain corticopetal cholinergic projections in attentional functions has been extensively investigated. For example, 192 IgG-saporin-induced loss of cortical cholinergic inputs was repeatedly demonstrated to result in a selective impairment in the ability of rats to detect signals in a task designed to assess sustained attention performance. The loss of cortical cholinergic inputs correlated highly with the decrease in the hit rate. Little is known about the functions of basal forebrain non-cholinergic neurons, particularly corticopetal GABAergic neurons, largely because of the absence of specific research tools to manipulate selectively this projection. As basal forebrain lesions produced with ibotenic acid were previously observed to potently destroy non-cholinergic, particularly GABAergic neurons while producing only moderate decreases in the density of cortical cholinergic inputs, the present experiment examined the effects of such lesions on sustained attention performance and then compared these effects with the immunohistochemical and attentional consequences of selective cholinotoxic lesions produced by intra-basal forebrain infusions of 192 IgG-saporin. In contrast to the selective decrease in hits previously observed in 192 IgG-saporin-lesioned animals, the attentional performance of ibotenic acid-lesioned animals was characterized by a selective increase in the relative number of false alarms, that is 'claims' for signals in non-signal trials. Analyses of the response latencies suggested that this effect of ibotenic acid was due to impairments in the animals' ability to switch from the processing of the response rules for signal trials to those for non-signal trials. As expected, 192 IgG-saporin did not affect the number of basal forebrain parvalbumin-positive neurons, that are presumably GABAergic, but decreased cortical acetylcholinesterase-positive fiber density by over 80%. Conversely, in ibotenic acid-lesioned animals, basal forebrain parvalbumin-positive cells were decreased by 60% but cortical acetylcholinesterase-positive fiber density was only moderately reduced (less than 25%). These data form the basis for the development of the hypothesis that basal forebrain GABAergic neurons mediate executive aspects of attentional task performance. Such a function may be mediated in parallel via basal forebrain GABAergic projections to the cortex and the subthalamic nucleus.

Effects of intralaminar thalamic lesions on sensory attention and motor intention in the rat: a comparison with lesions involving frontal cortex and hippocampus.

A self-paced serial reaction task was developed to differentiate between the effects of intralaminar thalamic lesions on sensory attention and intentional motor function. Results were compared for hippocampal and frontal cortical lesions to test for the possible involvement of pathways involving these parts of the brain in any impairments associated with the thalamic lesion. Lesions of the intralaminar thalamic nuclei affected response latency without affecting accuracy. This increase in latency was unaffected by variations in stimulus duration, even though this manipulation had a substantial effect on response accuracy. Intralaminar lesions did not affect the response to distracting stimuli or to manipulations of stimulus salience. Thus it seems unlikely that the effects of intralaminar lesions on motor function were related to sensory loss or attentional dysfunction. Hippocampal lesions had no significant effect on any measure of performance. Frontal cortical lesions were associated with an increase in latency comparable to the intralaminar group and also affected the accuracy of responding to brief stimuli or under conditions of reduced stimulus salience. These results are discussed in light of evidence that lesions of the intralaminar nuclei affect functions mediated by anatomically related areas of frontal cortex and striatum.

Effects of dorsal and ventral striatal lesions on delayed matching trained with retractable levers.

Recent evidence has suggested that thalamic amnesia results from damage to the intralaminar nuclei, an important source of input to striatum. To test the hypothesis that intralaminar damage disrupts functions mediated by striatum, we studied the effects of striatal lesions on a delayed matching task known to be affected by intralaminar lesions. Rats were trained to perform the task and given one of five treatments: sham surgery or a lesion of medial or lateral caudate/putamen, nucleus accumbens, or ventral striatum. Rats with ventral striatal lesions were impaired compared to all other groups. Rats with medial caudate/putamen or nucleus accumbens lesions were impaired compared to controls. The effects of ventral striatal lesions were sufficient to account for impairments in the accuracy and latency of delayed matching responses observed in previous studies of intralaminar and medial frontal cortical lesions. The ventral striatal lesions involved portions of ventral pallidum and thus it seems likely that they affected functions mediated by the nucleus accumbens as well as striatal areas of the tubercle. Serial reversal learning trained in the same apparatus with the same reinforcer was unaffected by all of the lesions. These results are discussed in terms of the roles of midline thalamic nuclei and of thalamo-cortico-striatal circuits in delayed conditional discrimination tasks.

A comparison of the effects of hippocampal or prefrontal cortical lesions on three versions of delayed non-matching-to-sample based on positional or spatial cues.

We trained rats to perform one of three versions of delayed non-matching-to-sample (DNMS): DNMS between two retractable levers in an enclosed operant chamber; varying-choice DNMS between two arms selected at random on every trial in an uncovered eight-arm radial arm maze; or recurring-choice DNMS between the same two arms on every trial in a covered radial maze (N=33/task). Rats with medial prefrontal cortical lesions showed delay-independent impairments on the retractable lever and recurring-choice tasks, but performed varying-choice DNMS normally. Rats with hippocampal lesions exhibited delay-independent impairments of the retractable lever task and delay-dependent impairments of both radial maze tasks. When rats trained initially to perform recurring choice DNMS were switched to varying choice DNMS, the impairments of both the prefrontal and hippocampal groups were reduced, although hippocampal animals remained significantly impaired. When rats trained initially to perform varying choice DNMS were switched to recurring choice DNMS, the impairment of the hippocampal group was exacerbated while the prefrontal group remained unimpaired. Thus training the prefrontal group to perform the varying choice task first seemed to protect from impairment when these rats were subsequently trained to perform recurring choice DNMS. This protection provides evidence against the possibility that factors related to proactive interference or to temporal discrimination can account for the effects of prefrontal lesions on delayed conditional discriminations involving two response alternatives in fixed locations.

Effects of chlordiazepoxide and FG 7142 on a rat model of diencephalic amnesia as measured by delayed-matching-to-sample performance.

The intralaminar thalamic nuclei (ILn) have been implicated as a critical site of pathology in amnesia. Lesions of the ILn have been found to produce behavioral effects comparable to benzodiazepine (BDZ) receptor agonists. We compared the effects of chlordiazepoxide (CDP), a BDZ agonist, and FG 7142, a partial inverse agonist at the BDZ receptor, in rats with thalamic lesions and in unlesioned controls. Delayed matching-to sample (DMS) performances were studied during treatment with ascending doses of CDP, counterbalanced trials with 2.5 mg/kg CDP and saline, ascending doses of FG 7142, and (for unlesioned controls only) counterbalanced trials with saline and higher doses of CDP. CDP had effects similar to the ILn lesion, decreasing response speed and percent correct responding in a delay-independent fashion. These effects were additive with the impairments associated with the ILn lesion. The effects of FG 7142 were more complex. At lower doses, it increased response speed without affecting response accuracy. At higher doses, it diminished both the speed and the accuracy of DMS responding. These results support the hypothesis that ILn lesions and BDZ agonists have similar effects on DMS performance. The biphasic effects observed for FG 7142 are consistent with other evidence that low doses of this drug enhance while higher doses impair memory performance. Although DMS accuracy was not improved, the enhancement observed for response speed provides evidence that partial inverse BDZ agonists have potential utility as treatments for cognitive impairments associated with amnesia.