Effects of specific brain lesions on the thermal responses of rats to D-amphetamine

A streptomycete strain (FERM-P1185), isolated from soil, secreted a slime on glucose-asparagine agar, and produced viscous growth in liquid media containing peptone as nitrogen source. A purified polysaccharide isolated from the culture broth was composed of glucose and mannose units (molar ratio 1-87:1). Periodate oxidation, Smith degradation, methylation analysis, infrared and 13c nuclear magnetic resonance spectra indicated that this mannoglucan had a linear structure consisting of alpha-1,3- and alpha-1,4-linked glucopyranose and mannopyranose units.     

Depression and self-medication with nicotine: The modifying influence of the dopamine D4 receptor gene.

This study evaluated whether there are genetic subgroups of depressed individuals who are more or less predisposed to engage in self-medication smoking practices. Smokers (N?=?231) completed self-report questionnaires of depression and smoking practices and were genotyped for the dopamine D4 (DRD4) gene. A significant interaction (DRD4 Genotype?×?Depression) was found for stimulation smoking and negative-affect reduction smoking. Specifically, these smoking practices were significantly heightened in depressed smokers homozygous for the short alleles of DRD4 but not in those heterozygous or homozygous for the long alleles of DRD4. These preliminary results suggest that the rewarding effects of smoking and the beneficial effects of nicotine replacement therapy for depressed smokers may depend, in part, on genetic factors involved in dopamine transmission. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of oral caffeine pretreatment on response to intravenous nicotine and cocaine.

Previous research suggests that under conditions of chronic daily caffeine administration, caffeine increases the effects of nicotine. Little is known about the effects of caffeine pretreatment on response to nicotine under infrequent caffeine administration conditions. The present study examined whether infrequent (not on consecutive days) acute oral caffeine administration alters subject-rated, physiological, and monetary value effects of intravenous nicotine in regular users of caffeine, tobacco, and cocaine. To determine the specificity of effects of caffeine on response to nicotine, the effects of caffeine administration on response to intravenous cocaine (another short-acting stimulant) were also studied. Fourteen (1 woman) volunteers participated in this 3–4 week, double-blind, inpatient study. Volunteers participated in 10 experimental conditions in pseudo-randomized order, in which oral caffeine (250 mg/70 kg) or placebo was administered 1 hr before an intravenous injection, consisting of nicotine (1 or 2 mg/70 kg), cocaine (15 or 30 mg/70 kg), or saline. Infrequent acute caffeine pretreatment attenuated the increase resulting from 2 mg/70 kg nicotine administration on ratings of “rush,” “good effects,” “liking,” “high,” and “drowsy/sleepy.” Caffeine had no significant effect on physiological response to nicotine. Caffeine had no significant effect on subject-rated and physiological response to cocaine, with the exception that caffeine significantly augmented blood pressure response to cocaine. In contrast to the previous research using chronic caffeine maintenance, these data suggest that infrequent acute caffeine administration may attenuate nicotine effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The influence of nicotine dose and nicotine dose expectancy on the cognitive and subjective effects of cigarette smoking.

This study investigated the independent and interactive effects of nicotine dose and nicotine dose expectancy on smoking outcomes using a 2 (given nicotine vs. placebo) × 2 (told nicotine vs. placebo) Balanced Placebo Design (BPD). Smokers (N = 148) completed the Rapid Visual Information Processing Task (RVIP) and measures of smoking urge, mood, and cigarette ratings (e.g., satisfying) after smoking a nicotine or placebo cigarette crossed with instructions that the cigarette contained either nicotine or no nicotine. Nicotine cigarettes (0.6 mg nicotine) produced better sustained attention performance than placebos as indicated by RVIP reaction time, hits, and sensitivity (A′). Nicotine cigarettes also produced better mood and greater rewarding subjective effects of the cigarettes on 11 of 11 dimensions compared to placebos. Nicotine instructions resulted in fewer RVIP false alarms, better mood, and greater rewarding subjective effects of the cigarettes on 9 of 11 dimensions compared to placebo instructions. Nicotine dose by nicotine dose expectancy interactions were also observed for urge and tension-anxiety, such that the dose expectancy manipulation produced differential effects only among those who smoked placebo cigarettes. In contrast a significant interaction for self-reported vigor-activity demonstrated that the dose expectancy manipulation produced effects only among those who smoked nicotine cigarettes. This study provides additional evidence that nicotine improves cognitive performance, and provides initial evidence that denicotinized cigarettes smoked under the guise that they contain nicotine influence cognitive performance, albeit with less robust effects than nicotine. These data may inform the development of expectancy-based interventions for tobacco dependence. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The effect of cocaine and D-amphetamine on punished responding

Various dosages of d-amphetamine (0.1, 0.5, 2.5 mg/kg) and of cocaine (5.0, 20, 40 mg/kg) were administered i.p. to each of 7 rats trained in an experimentally induced conflict procedure. Sessions were 1 hr in duration and consisted of five 12 min periods; responding was reinforced with food on a F124 sec schedule of reinforcement during each period; however, in periods 2 and 4 each response was followed by the application of footshock. Significant increase in responding did not occur in any period following any of the pretreatments. Cocaine (5.0, 20 mg/kg) and d-amphetamine (0.5, 2.5 mg/kg) significantly decreased responding in both punished and unpunished periods. Following these treatments the rate of responding in punished and unpunished components was not significantly different. This suggest that psychomotor stimulants may not selectively increase anxiety, at least at dosages which are not at the same time anorexic.     

Electrolytic lesions of the nucleus accumbens enhance locomotor sensitization to nicotine in rats.

Electrolytic lesions of the medial core of the nucleus accumbens (NAc) in male Long-Evans rats increased spontaneous locomotion, enhanced the locomotor stimulating effect of acute 5.0 mg/kg cocaine, enhanced the development and subsequent expression of locomotor sensitization produced by repeated injections of 0.4 mg/kg nicotine but not 7.5 mg/kg cocaine, and enhanced the expression of conditioned locomotion. Given that 6-hydroxydopamine lesions of the NAc typically have effects on locomotor-related processes that are opposite of those produced by electrolytic and excitotoxic lesions, these data are consistent with a hypothesis that the NAc output, especially from the core, inhibits a variety of such processes and that the DA input to the NAc enhances these processes by inhibiting this inhibitory output. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alpha2-adrenergic control of dopamine overflow and metabolism in mouse striatum

The effects of the alpha2-adrenoceptor drugs, medetomidine and atipamezole, on dopamine overflow evoked by low (6 Hz-10 s) and high (50 Hz-4 s) frequency electrical stimulation of the median forebrain bundle were studied in striatum of BALB/C mice anaesthetized with chloral hydrate with fast in vivo voltammetry techniques. The effects of these drugs on the basal concentrations of dopamine metabolites were also investigated by means of differential pulse voltammetry. Medetomidine dose dependently decreased dopamine overflow in nucleus accumbens in the dose range 5-100 microg/kg, s.c. This effect was seen only at low frequency stimulation and reached 85% at a dose of 100 microg/kg. Medetomidine also decreased the basal concentration of striatal homovanillic acid. This effect did not exceed 35%. Atipamezole antagonized the inhibitory effects of medetomidine on the dopamine overflow. but showed no effect itself. We suggest that alpha2-adrenoceptors in dopaminergic terminal fields in the mouse striatum are involved in the regulation of dopamine release at physiological stimulation frequencies.     

Subjective responses to nicotine in smokers may be associated with responses to caffeine and to alcohol.

Sensitivity in responses to one drug may relate to sensitivity to other drugs, suggesting broad individual differences in characteristic responsivity across drugs. Data from two separate studies of smokers were reanalyzed to examine associations between acute subjective and cardiovascular effects of nicotine vs. caffeine and between nicotine vs. alcohol. Typical intakes of cigarettes, alcohol, and caffeine were included as covariates when they were correlated with the responses of interest. Significant associations between nicotine and caffeine were seen for most of the subjective measures and for blood pressure responses. Fewer significant associations were observed between nicotine and alcohol. Responses associated between nicotine and both of the other drugs tended to reflect psychomotor stimulation. These results suggest that smokers who are more responsive to some of nicotine's subjective and blood pressure effects are also more sensitive to the same effects of caffeine and, to a lesser extent, of alcohol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lobeline and nicotine evoke [3H]overflow from rat striatal slices preloaded with [3H]dopamine: differential inhibition of synaptosomal and vesicular [3H]dopamine uptake

Lobeline is currently being developed as a substitution therapy for tobacco smoking cessation. Activation of CNS dopamine (DA) systems results in the reinforcing properties of nicotine. The present study compared the effects of lobeline and nicotine on rat striatum. Both lobeline and nicotine evoked [3H]overflow from striatal slices superfused in the presence of pargyline and nomifensine in the buffer. Marked DA depletion (42-67%) and a concomitant 2-fold increase in dihydroxyphenylacetic acid (DOPAC) in slices superfused with high concentrations (30-100 microM) of lobeline were observed. The effect of nicotine (10 microM) was inhibited in a concentration-dependent manner by mecamylamine (1-100 microM). However, lobeline (0.1-100 microM)-evoked [3H]overflow was calcium-independent, and was not antagonized by mecamylamine (1-100 microM), suggesting a mechanism of action other than stimulation of nicotinic receptors. Lobeline inhibited [3H]DA uptake into synaptosomes (IC50 = 80 +/- 12 microM) and vesicles (IC50 = 0.88 +/- 0.001 microM), whereas nicotine (< or =100 microM) did not inhibit synaptosomal or vesicular [3H]DA uptake. In the absence of pargyline and nomifensine in the buffer, endogenous DA was detected in superfusate only in those slices exposed to the highest concentration (100 microM) of lobeline. However, endogenous DOPAC concentration was increased in a concentration-dependent manner, indicating that lobeline exposure resulted in increased cytosolic DA which was rapidly metabolized to DOPAC. Under these conditions, lobeline (10-100 microM) also significantly depleted (66-85%) DA content; however, no change in DOPAC content was observed. The results suggest that, unlike nicotine, lobeline increases DA release by potent inhibition of DA uptake into synaptic vesicles, and a subsequent alteration in presynaptic DA storage.     

The effects of morphine, nicotine and epibatidine on lymphocyte activity and hypothalamic-pituitary-adrenal axis responses

Acute administration of morphine alters various neuroendocrine and immune parameters via opioid receptors located within the central nervous system. Similar effects have been reported after systemic nicotine treatment. To examine the possible relationship between opioid and nicotinic receptor activation on the immune system, we compared the effects of morphine with both nicotine and the highly selective nicotinic agonist, epibatidine. Male Sprague-Dawley rats were treated with either morphine (10 mg/kg, s.c.), nicotine (2.85 mg/kg, s.c. = 1 mg/kg freebase), or epibatidine (5 microg/kg, s.c.) and sacrificed 2 hours later. Each drug increased plasma corticosterone levels and decreased the magnitude of the peripheral blood lymphocyte proliferation response to the T cell mitogen concanavalin A. None of the treatments had a significant effect on splenic or thymic lymphocyte responses. The effects of nicotine treatment were dose-dependent. Pretreatment with the quaternary ganglionic antagonist chlorisondamine (0.5 mg/kg, i.p.), completely blocked the effect of epibatidine on blood lymphocytes without altering the elevation of corticosterone levels. Although naltrexone (10 mg/kg, s.c.) blocked all effects of morphine, the effects of epibatidine were not blocked by the opioid receptor antagonist. Furthermore, in contrast to morphine (), central injection of neither nicotine (30 or 240 nmol) nor epibatidine (5, 50, or 500 ng) altered blood lymphocyte responses. These results suggest that, like morphine, nicotinic agonists decrease blood lymphocyte proliferation responses, apparently independent of elevated corticosterone. However, unlike morphine, nicotinic agonists appear to act predominantly at peripheral receptors, suggesting that nicotinic receptors are downstream of opioid receptors in a centrally mediated opioid-induced immunomodulatory pathway.     

Effects of repeated nicotine pre-treatment on mesoprefrontal dopaminergic and behavioral responses to acute footshock stress

The effects of acute and repeated nicotine administration on the stress response of rat mesoprefrontal dopaminergic pathways were examined. Rats were given daily injections of nicotine (0.15 or 0.60 mg/kg, s.c., freebase) or saline for 4 days, then challenged with either nicotine or saline. A regimen of inescapable electrical footshocks or no footshocks was then administered. Thirty minutes after final injection, rats were sacrificed, brains removed and dopamine (DA) and its metabolite dihydroxy-O-phenylacetic acid (DOPAC) were extracted from medial prefrontal cortex (mPFC), nucleus accumbens septi (NAS) and dorsolateral striatum and quantified by high performance liquid chromatography with electrochemical detection. Acute administration of low dose nicotine (0.15 mg/kg) produced an increase in DA utilization (increased DOPAC/DA ratio) in mPFC and NAS, but not striatum. High dose nicotine (0.60 mg/kg) produced activation in NAS, but not mPFC or striatum. Repeated low dose nicotine pre-treatment produced tolerance to the effects of nicotine challenge in the mPFC, and reduced its effects in NAS. Footshock stress preferentially increased DA utilization in mPFC and associated footshock stress-induced immobility responses, and these were reduced by low, but not high, dose repeated nicotine pre-treatment. Further, a single dose of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (MCA) 30 min prior to nicotine challenge dose-dependently blocked the reduction of mesoprefrontal DA stress responsivity and immobility responses produced by repeated nicotine pre-treatment. These results indicate that: (1) there are dose-dependent differential effects of acute and repeated nicotine pre-exposure on regional DA utilization; (2) low, but not high, dose repeated nicotine reduces both the mesoprefrontal DA and behavioral effects of acute footshock stress; and (3) these effects of repeated nicotine may depend on mecamylamine-sensitive nAChR stimulation. These results may have relevance to acute stress and nicotine dependence, particularly in schizophrenic disorders, which have high prevalence rates of co-morbid nicotine dependence, stress-induced symptom exacerbation and prefrontal cortical dysfunction.     

The influence of transdermal nicotine on tobacco/nicotine abstinence and the effects of a concurrently administered cigarette in women and men.

Transdermal nicotine (TN) is an efficacious smoking cessation pharmacotherapy thought to work, in part, by attenuating the effects of tobacco/nicotine abstinence and the effects of concurrently smoked cigarettes. Clinical trials suggest that TN may be less efficacious for women. This study explored the possibility of TN-related gender differences in ≥8 hour abstinent smokers (54 women, 70 men) who completed four within-subject, double-blind, placebo-controlled sessions corresponding to 0, 7, 14, and 21 mg TN. In each approximately 6.5-hr long session participants smoked an own-brand cigarette 4 hours after TN administration and physiological and subjective outcomes were examined throughout each session. Results revealed that TN suppressed some signs and symptoms of tobacco abstinence and attenuated some effects of smoking, and these effects were not dependent on gender. Women were more sensitive to the direct effects of nicotine (e.g., ratings of Nauseous) and, independent of TN dose, self-administered less nicotine when smoking and rated smoking as less rewarding. Thus, although this study does not shed light on clinical observations that TN is less effective for women, results suggest that TN might need to be combined with other interventions to supplement its effects on tobacco/nicotine abstinence and concurrent smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

From approach to inhibition: The influence of power on responses to poor performers.

This article examines how relative differences in power affect responses to poor performers in organizations. We predicted that higher power individuals would engage in approach-related behaviors, whereas lower power individuals would be inhibited when responding to poor performers. Results from a scenario study and a field study generally supported this prediction, indicating that power was positively related to training or confronting a poor performer and negatively related to compensating for or rejecting a poor performer. A second scenario study investigated the effect of the interaction of power and emotion on individual responses to poor performers. Results showed that the type of emotion expressed moderated the effect of power on inhibition-related responses. We discuss implications for managing poor performers with relative power differences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of ZnCl2 pretreatment on behavioral and histological responses to kainic acid in rats

Kainic acid evokes behavioral convulsions and causes lesions in hippocampal pyramidal cell layers in rats. The effects of ZnCl2 pretreatments on these events were examined. Rats were given ZnCl2 (35 mg/kg, subcutaneously (s.c.)) 15 min prior to kainic acid administration (12 mg/kg, intraperitoneally (i.p.)). Another group of animals was given an additional dose of ZnCl2 (35 mg/kg, i.p.) 24 h prior to the s.c. ZnCl2 and i.p. kainic acid. All rats that received kainic acid, whether saline controls or ZnCl2 pretreated, experienced wet dog shakes (WDS) and convulsions. No significant differences were seen between groups in number or latency of WDS or convulsions. Two days after behavioral data were collected, the brains were perfused and the extent of lesioning among hippocampal CA1 and CA3 pyramidal cells was quantified. A single dose of ZnCl2 had either no effect or a slight protective effect on cell lesioning induced by kainic acid. However, lesioning was more pronounced in animals treated twice with zinc. It is concluded that zinc, co-administered with kainic acid, augments kainate cytotoxicity when the dose and timing of zinc exposure are within a critical period.     

Hemodynamic and regional blood flow responses to nicotine at rest and during exercise

We hypothesized that nicotine compromises cardiovascular responses to dynamic exercise. Hemodynamic variables were measured in conscious miniswine before and at 2 min of nicotine infusion (20 micrograms.kg-1.min-1; i.a.; N = 6) during resting conditions. Mean arterial pressure elevations (MAP; 14%) and plasma nicotine concentrations (49 +/- 7 ng.ml-1) were similar to those elicited by cigarette smoking in humans. In addition, nicotine increased systemic vascular resistance (SVR; 56%), the heart rate x systolic blood pressure product (RPP; 11%), and regional vascular resistance in the left-ventricular, renal, and splanchnic circulations, while cardiac output decreased (CO; 23%) and skeletal muscle blood flow and vascular resistance were unaffected. Plasma norepinephrine and epinephrine increased by approximately 30% and 90%, respectively. On separate days, the same hemodynamic responses were measured before and at 20 min of treadmill running during vehicle or nicotine infusion for the last 2 min of exercise (N = 10). Nicotine increased MAP (6%), SVR (14%), and RPP (3%), and elevated vascular resistance in the proximal colon and pancreas. Moreover, compared to exercise + vehicle, norepinephrine and epinephrine increased by approximately 13% and 24%, respectively, during exercise + nicotine infusion. These findings suggest that the detrimental effects of nicotine observed at rest are minimized during exercise. Nicotine's effects may be reduced during exercise by competition from local vasodilators in the heart and active musculature, and/or by differing activation of sympathetic nerve activity.     

Effects of GBR 12909 on locomotor activity and dopamine turnover in mice: comparison with apomorphine

31 patients with schizophrenic adolescent paranoid syndrome were treated by Leponex-Sandoz after the establishing of the therapeutic indications. We did not observe any considerable side effects. We observed the regression of positive symptoms at 19-day of the treatment and the regression of negative symptoms at 23-day of the therapy. We conclude that Leponex-Sandoz is effective and safe medication in the treatment of adolescent schizophrenic paranoid syndrome.     

N-methyl-D-aspartate and dopamine receptor involvement in the modulation of locomotor activity and memory processes

In this study we report on the effects of N-methyl-D-aspartate (NMDA)- and dopamine (DA)-receptor manipulation on the modulation of one-trial inhibitory avoidance response and the encoding of spatial information, as assessed with a non-associative task. Further, a comparison with the well-known effects of the manipulation of these two receptor systems on locomotor activity is outlined. It is well assessed that NMDA-receptor blockage induces a stimulatory action on locomotor activity similar to that exerted by DA agonists. There is evidence showing that the nucleus accumbens is involved in the response induced by both NMDA antagonists and DA agonists. We show results indicating a functional interaction between these two neural systems in modulating locomotor activity, with D2 DA-receptor antagonists (sulpiride and haloperidol) being more effective than the D1 antagonist (SCH 23390) in blocking MK-801-induced locomotion. A different profile is shown in the effects of NMDA antagonists and DA agonists in the modulation of memory processes. In one-trial inhibitory avoidance response, NMDA antagonists (MK-801 and CPP) impair the response on test day, while DA agonists exert a facilitatory effect; furthermore, sub-effective doses of both D1 (SKF 23390) and D2 (quinpirole) are able to attenuate the impairing effect in a way similar to that induced by NMDA antagonists. The effects of NMDA- and DA-acting drugs on the response to spatial novelty, as assessed with a task designed to study the ability of animals to react to discrete spatial changes, are in good accord with the effects observed on passive avoidance. The results show that NMDA as well as DA antagonists, at low doses, selectively impair the reactivity of mice to spatial changes. In a last series of experiments, the possible role of NMDA receptors located in the nucleus accumbens was investigated regarding reactivity to spatial novelty. The experiments gave apparently contrasting results: while showing an impairing effect of focal administrations of NMDA antagonists in the nucleus accumbens on reactivity to spatial novelty, no effect of ibotenic acid lesions of the same structure was observed.     

Asymmetrical increases in dopamine turn-over in the nucleus accumbens and lack of changes in locomotor responses following unilateral dopaminergic depletions in the entorhinal cortex

Purified integrin alpha v beta 3 was used in solid-phase binding studies with chimeric hepatitis B cores which carry the RGD-containing loop of VP1 protein of the foot-and-mouth disease virus (FMDV). High levels of specific binding between the integrin and the particles were detected by enzyme-linked immunosorbent assays. The binding was Mn2+ cation dependent and could be competed with fibronectin, vitronectin, and the peptide GRGDSPK. Particles in which the RGD motif had been mutated to RGE failed to bind, indicating that the chimeric cores bound specifically to the ligand binding site of integrin alpha v beta 3. Electron micrographs showed several individual alpha v beta 3 molecules bound to the surface of each chimeric particle. Collectively, these data constitute firm evidence that the RGD-containing loop of FMDV is critical for binding to alpha v beta 3 and provide support for identification of alpha v beta 3 as a potential cellular receptor for FMDV.     

Chronopharmacological effects on nicotine repeated administration on heart rate, body temperature and locomotor activity circadian rhythms in rats

The aim of this study was to compare morning and evening repeated nicotine administration on the circadian rhythms of heart rate (H), body temperature (T) and locomotor activity (A) in unrestrained rats by using implanted radio-telemetry transmitters. The study was divided into three 7-day periods: a control period (P1), a treatment period (P2) and a recovery period (P3). During P2, four rats received nicotine (1mg.kg(-1)) subcutaneously at 09.00 h and four rats received nicotine in the same conditions at 21.00 h. For P1, P2 and P3, a power spectrum analysis was applied in order to determine the dominant period of rhythmicity. If H, T and A circadian rhythms were detected, the characteristics of these rhythms were determined by cosinor analysis, expressed as means+/-SEM and compared by ANOVA. Our results indicated: (1) a lack of detection of A circadian rhythm during P2 for the morning group while H and T circadian rhythms were detected for the morning and evening group whatever the period. (2) alterations of mesors, amplitudes and acrophases of H and T circadian rhythms for the morning and evening group during P2 and alterations of mesor, amplitude and acrophase of A circadian rhythm for the evening group. Furthermore these alterations were significantly different for the morning and evening group during P2. These results showed that the time of administration of nicotine differently affect H, T and A rhythms. The authors suggest that these effects can be mediated by central cholinergic and/or monoaminergic mechanisms.     

The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates

The humoral and cell-mediated immune responses to subsequent allografts were determined in primate recipients after concordant xenotransplantation as a bridge to allotransplantation. Heterotopic heart transplants (n = 4) were performed from cynomolgus monkeys into ABH type-matched olive baboons followed 2 weeks later by allotransplantation from ABH type-matched baboon donors. Allografts were explanted at 8 weeks. All recipients underwent splenectomy at the time of xenotransplantation and received immunosuppression with cyclosporine, azathioprine, and methylprednisolone. Concordant xenotransplantation in these primates did not induce humoral or cell-mediated immune responses that jeopardized subsequent allografts. The degree of xenospecific immune reactivity, as determined by specific cytotoxicity of recipient T-cell lines derived from the xenograft and extent of histologic xenograft rejection, did not predict the severity of subsequent allograft rejection. In two of the four recipients, xenotransplantation induced an alloreactive humoral response against antigens expressed by the B cells of more than 50% of members from a panel of 12 unrelated baboons. In all recipients, priming with xenogeneic splenocytes in vitro induced an accelerated proliferative T-cell response to allogeneic lymphocytes from 16% of this panel. This study affirms the role of concordant xenografts as appropriate biologic bridges to human allotransplantation. However, our results suggest that xenoreactive baboon memory CD4 T cells may recognize major histocompatibility complex class II--like structures shared between the xenogeneic and allogeneic targets. The potential allorecognition induced by a xenograft may affect the process of subsequent allograft donor selection.