Zoonotic assemblages of Giardia duodenalis in captive non-human primates from the largest zoo in Slovakia.

Only a few studies based on multilocus characterization have been conducted on the molecular epidemiology of Giardia duodenalis in captive nonhuman primates (NHPs). The present article provides the first report on the occurrence of G. duodenalis in the ring-tailed lemur (Lemur catta) and barbary macaque (Macaca sylvanus) kept in the zoo in Kosice, Slovakia. All samples were examined by flotation technique, with total prevalence of 17.4% (4/23). The microscopically positive samples were assayed by nested PCR and consecutively sequenced at ß-giardin (bg), glutamate dehydrogenase (gdh) and triosephosphate isomerase (tpi) genes. Positive isolates were recognized as assemblage B and sub-assemblage BIV and subtype WB8 were confirmed. The identification and genotyping of this parasite in Slovakia, may help to better understand the epidemiological situation in Europe about the circulation of G. duodenalis zoonotic assemblages in NHPs.

Cerebral monitoring during carotid endarterectomy using transcranial cerebral oximetry.

OBJECTIVE: This study aimed to evaluate the outcomes of carotid endarterectomies (CEA) performed using transcranial cerebral oximetry as cerebral monitoringMETHODS: This single-center study included patients treated surgically for significant stenosis of the internal carotid artery (ICA) from January 2012 to December 2017RESULTS: Of the 654 patients, 267 were asymptomatic, and 387 were symptomatic. Eversion CEA was performed in 64.8 %, and patched conventional CEA in 35.2 % of all patients. Totally 11.4 % of all patients had a shunt inserted; all patients with the inserted shunt had the conventional pathed CEA. Severe postoperative complications occurred in 1.5 % of asymptomatic patients and 2.6 % of symptomatic patients. The stroke and death ratio in the shunted group was 2.7 %, and in the non-shunted group, 2.1 % (p = 0.7). We found no significant difference in severe postoperative complications between the shunted and non-shunted group. Further, we found the male gender (p = 0.005), coronary artery disease (p = 0.01), and ongoing smoking (p = 0.003) to be significantly associated with neurological symptoms of the ICA stenosis. We also confirmed current tobacco smoking to be significantly associated with the occurrence of postoperative stroke and death (p = 0.005)CONCLUSION: We found transcranial cerebral oximetry to be reliable in the determination of shunt insertion (Tab. 6, Ref. 26).

Impacto de un programa de capacitación para la prevención de infecciones intrahospitalarias en un hospital general / Impact of a training program for the prevention of infections in a general hospital nosocomial

Objetivo: Incrementar la adherencia del personal de salud a tres prácticas de control de infecciones a través de una intervención educativa. Material y metodología: Durante 11 meses, 440 trabajadores de salud recibieron capacitación en control de infecciones. Se aplicó la capacitación de instrucción suplementaria basada en vídeos (VSI), incidiendo en el lavado de manos, uso de respirador N95 y prevención de cortes y punciones con instrumental. Se realizó una evaluación a los tres y a los seis meses post-intervención. Resultados: Se obtuvo en el personal de salud un incremento en la adecuada técnica del lavado de manos del 7% al 78% (p<0,05), en el uso adecuado del respirador N95 del 0% al 81,5% (p<0,01) y se observó una disminución en la proporción de cortes y punciones entre los internos de medicina del 0,20 al 0,44% (p<0,006). No se encontró diferencia en otros grupos poblacionales. Conclusión: La metodología VSI tiene efectos positivos en la adopción de prácticas de control de infecciones en personal de salud (AU)

Objective: To increase the adherence of health care workers to three infections control practices through an educational intervention. Methods: 440 health care workers were trained in infection control during the period of 11 months. The methodology training Video-based Supplemental Instruction (VSI) affecting three infection control practices: Wash hands, N95 respirator use and prevention of needle stick accidents. They were evaluated 3 and 6 months post-intervention. Results: Obtained health care workers increased from 7% to 78% (p<0.05) in the proper hand washing technique, from 0% to 81.5% in the proper use of N95 respirator and was observed decrease in the proportion of sharp accidents in medical interns trained 0.20 vs. 0.44 (p<0.006). No difference was found in other populations intervened. Conclusion: The methodology VSI has positive effects on the adoption of infection control practices in health care workers (AU)

Toll-like receptors TLR1, TLR2 and TLR4 gene mutations and natural resistance to Mycobacterium avium subsp. paratuberculosis infection in cattle.

Toll like receptors (TLRs) are a class of pattern recognition receptors belonging to the innate immune system. Mutations in the protein coding region of TLRs are associated with altered responsiveness to pathogen-associated molecular patterns (PAMPs). A search was performed for novel mutations in bovine TLR1, TLR2 and TLR4 genes associated with the Mycobacterium avium subsp. paratuberculosis (MAP) infection. The work was also focused on the assessment of linkage between well known mutations in TLR genes (TLR2: Arg677Trp, Pro681His and Arg753Gln; TLR4: Asp299Gly and Thr399Ile), and the susceptibility of cattle to MAP infection. Detection of MAP infection in cattle population (n=711) was based on IS900 PCR, which revealed 22.50% (n=160) MAP positivity. Known mutations in TLR2 and TLR4 genes were not found in cattle population. A novel mutation Val220Met was associated (Odd's ratio, OR-3.459) with increased susceptibility to MAP infection. Toll/interleukin-1 receptor (TIR) domain of TLR2 was screened for the presence of mutations, wherein a novel Ile680Val mutation was linked with MAP infection. In silico analysis of the bovine TLR4 ectodomain (ECD) revealed the polymorphic nature of the central ECD and irregularities in the central LRR motifs. LRR11 of the TLR4 showed five missense mutations possibly linked with the increased susceptibility to MAP infection. The most critical position that may alter the pathogen recognition of TLR molecule was 4th residue downstream to LRR domain. Two such missense mutations in TLR4 (Asp299Asn downstream to LRR11, and Gly389Ser downstream to LRR15) were associated with MAP infection. Briefly, the work describes novel mutations in the bovine TLRs and presents their association with the MAP infection.

Anxiogenic-like effects of opiate withdrawal seen in the fear-potentiated startle test, an interdisciplinary probe for drug-related motivational states.

RATIONALE: Anxiety-like effects may be universal to withdrawal from drugs of abuse. The study of withdrawal would benefit from the acoustic startle response (ASR), a discrete, cross-species reflex which is increased by fear-related states. However, existing reports of opiate-related effects on baseline ASR have not validated ASR as a measure of drug-related motivation. OBJECTIVE: The effects of opiate treatment and withdrawal were examined using fear-potentiated startle, a startle test more sensitive to fear than baseline changes. METHODS: Fear-conditioned rats were treated with Alzet osmotic pumps delivering 0.25 mg/kg per day fentanyl or placebo pumps. Experiment I examined changes before and during opiate treatment on locomotor activity and baseline, prepulse inhibition, and fear-potentiated startle. Experiment 2 examined the same responses during withdrawal precipitated after 4-7 days of treatment using IV naloxone. RESULTS: Experiment 1 revealed an attenuated fear-potentiated startle on the first test after the start of fentanyl treatment (4 h); this was not seen on subsequent tests and suggested tolerance to this acute effect. Experiment 2 found an enhancement of fear-potentiated startle precipitated in fentanyl-treated rats after injection of 0.025 and 0.16 mg/kg naloxone; this was not seen at 1 mg/kg naloxone, even though more physical withdrawal signs were most prevalent at this dose. In neither experiment did locomotor activity, baseline ASR, or prepulse inhibition of the ASR show any treatment effect. CONCLUSIONS: Fear-potentiated startle may provide a specific and valid measure of anxiety-like effects of drug withdrawal. Discussed were conditions needed to see this effect and the relevance of the findings for different mechanisms of withdrawal discomfort.

[The long-term evaluation of artificial myoplastic anus and artificial classical anus based on manometric and radiological examinations]. / Odlegla ocena sztucznego odbytu mioplastycznego i wytworzonego klasycznie na podstawie badan manometrycznych i radiologicznych.

The aim of this study was comparative evaluation of the pressure profile in the artificial myoplastic anus and the one created by the use of classical method. Radiological examinations of the colon by the use of the contrasting agent were performed in all patients in each group. In the group of patients with artificial myoplastic anus radiological examinations showed the narrowing of the lumen 4-7 cm in length in all patients. Above the narrowing the widening of the lumen was present. Reflexive flow of the contrasting agent from the colon was not present. In the group of patients with the artificial classical anus the narrowing of the terminal part of the colon was not noticed in the radiological examination. In all patients the reverse flow of the contrasting agent through the artificial anus was observed. Patients with the artificial myoplastic anus created by the use of pedunculated fold of the muscular coat of the colon have much higher average pressures around the myoplastic sphincter than in the presphincteric area, while the patients with the artificial classical anus did not present the area with the increased pressure in the terminal part of the colon. The possibility of preventing uncontrolled defecation and flatulence by the patients with the artificial myoplastic anus is related to the repeatedly higher pressures around the sphincter than in the presphincteric area, which do not decrease as the time passes by after the surgery.

Appetitve effects of drug cues modelled by pictures of the intake ritual: generality of cue-modulated startle examined with inpatient alcoholics.

RATIONALE: A cue-modulated startle test recently confirmed that smoking cues in smokers may not be withdrawal-like and aversive as traditionally believed. OBJECTIVE: Analogous tests were applied to alcohol cues in inpatient alcoholics. METHODS: Twenty-six withdrawn alcoholics (18 men) were examined. Alcohol-related pictures were compared to standardised pleasant, neutral or unpleasant control scenes using an acoustic startle test and measures of pleasure, arousal and desire for alcohol. RESULTS: Pictures depicting preparation for drinking (cues) were different from unpleasant control pictures and similar to pleasant pictures but only on the startle test; no differential effects were found for alcohol craving and mixed motivational effects were reported subjectively. The effects were not due to arousal and control pictures depicting post-drinking events showed less effect than the alcohol cues. CONCLUSIONS: New techniques of measuring drug cue motivation indicate that drug cues may have incentive properties in individuals in treatment for alcoholism.

Appetitive nature of drug cues confirmed with physiological measures in a model using pictures of smoking.

RATIONALE: In smokers, pictures of smoking that increase desire for a cigarette are described as pleasant rather than unpleasant. This suggests that these smoking cues may be appetitive and not withdrawal-like or aversive as held by traditional theories of drug cue formation. OBJECTIVE: Cues for smoking were examined using physiological measures of motivational valence. METHODS: Non-deprived smokers, deprived smokers and deprived smokers who expected to smoke (n=54) viewed a computer screen presenting experimental and control scenes (experiment 1). The acoustic startle reaction and activity of the corrugator and the zygomatic facial muscles were then measured after onset of smoking cues and standardized pleasant, neutral or unpleasant control scenes. Individuals who never smoked (n=18) were also used to test for cue effects on startle (experiment 2). RESULTS: No evidence was found that smoking cues were aversive in smokers. The smoking cues affected the startle responses and corrugator activity in a way similar to that of pleasant control material but significantly different from that of unpleasant material; the cue effects on zygomatic activity was most similar to that of neutral material. The general pattern of effects was not influenced by overnight smoke deprivation, expectancy to smoke or smoke repletion, but it was different in never smokers where the smoking scenes were found to be similar to unpleasant control scenes. CONCLUSIONS: Nonsubjective measures of motivational valence further suggest that drug cues are conditioned stimuli having appetitive effects. Startle response modulated by drug cues may be useful for probing motivational processes underlying dependence in the human.

Topography of sham and real puffing examined using a paced smoking regimen.

Topographical patterns of normal puffing on a cigarette may be reflected in the topographical patterns of sham puffing (Morris & Gale, 1994). To test further the possibility of measuring behavior associated with cigarette smoke self-administration without actual smoke intake, we compared sham and real puffing using a paced smoking regimen under different levels of smoke deprivation. Cigarette smokers were instructed to draw and inhale six times on their unlit and then subsequently on their lit cigarette. Intensity, maximum, area and duration of puffs were lower for sham as opposed to real puffing; however, sham and real puffing showed parallel changes in response to deprivation, and significant positive correlations were found between the two puffing conditions for puff intensity, maximum and area. Therefore, we confirmed a similarity of real puffing with puffing under placebo conditions. Discussed was smoking as an automatic motor behavior.

Modulation of craving by cues having differential overlap with pharmacological effect: evidence for cue approach in smokers and social drinkers.

RATIONALE: An increased risk of drug intake produced by drug cues may reflect the fact that the cues are withdrawal-like or aversive, reflecting a conditioned adaptation to the drug's acute effects. More recent work suggests that they may also be appetitive, signalling the goal characteristics of drug taking. OBJECTIVE: These opposing mechanisms were tested in dependent smokers and in social drinkers by examining the motivational nature of drug cues that overlap differentially with the acute effects of the drug. METHODS: Pictures of different phases of smoking or alcohol drinking were presented to deprived and non-deprived smokers, to never smokers and non-deprived smokers or to social drinkers. Desire for cigarettes or alcohol and momentary pleasure and arousal were measured after viewing an experimental picture or a pleasant, neutral or unpleasant control scene. RESULTS: High desire for smoking was evoked by pictures of preparation for and actual smoking but not by scenes of the end of smoking, although the latter were best correlated with acute drug effect. This pattern was not affected by overnight smoke deprivation, it was seen in different smokers but not in never-smokers and it was replicated in social drinkers using pictures of alcohol consumption. Moreover, scenes evoking high desire to consume did not evoke states of momentary unpleasantness and they were seen as relaxing and not arousing. Control pictures had a minimal effect on desire to consume. CONCLUSIONS: In line with incentive models of drug cues, cues based on pictures of drug intake may be conditioned stimuli encoding cue approach and preparation for consumption.

Conditioned responses elicited by experimentally produced cues for smoking.

Several theories of drug-craving postulate that a signal for drug elicits conditioned responses. However, depending on the theory, a drug cue is said to elicit drug similar, drug compensatory, positive motivational, and negative motivational effects. Since animal data alone cannot tease apart the relative importance of different cue-related processes in the addict, we developed and examined a model of drug cues in the human based on a two-sound, differential conditioning procedure using smoking as the reinforcer. After multiple pairings of a sound with smoking, there was a preference for the smoking cue on a conditioned preference test. The acute effects of smoking (increased heart rate, respiration rate, skin conductance level, skin conductance fluctuations, EEG beta power and trapezius EMG, decreased alpha power) were not affected by the smoking cue, although subjects drew more on their cigarette in the presence of the smoking cue than in the presence of a control cue. Moreover, the cue did not change baseline behaviour except for a possible increase in EEG beta power and an increase in trapezius EMG at about the time when smoking should have occurred. The findings confirm the value of experimental models of drug cues in the human for comparing different cue phenomena in the dependent individual. They indicate that an acquired signal for drug in the human may elicit incentive motivational effects and associated preparatory motor responses in addition to possible conditioned tolerance.

Dependence on smoking and the acoustic startle response in healthy smokers.

Recent data from nicotine-dependent rats (14) and healthy smokers (18) would suggest that nicotine withdrawal modulates the acoustic startle reflex in a way similar to that of fear (5,20). We examined this directly using nonsmokers and healthy smokers who had no deprivation, brief deprivation (2-3 h), or prolonged deprivation (15 h). Groups differences in heart rate (HR), alveolar carbon monoxide (CO) levels, and desire and craving for cigarettes confirmed the presence of smoking withdrawal. However, there were no significant differences in the magnitude of the baseline startle response among the differently deprived smokers or between the smokers and the nonsmokers. Subsequent startle tests were carried out in the smokers during repeated sequences of preparing a cigarette for smoking (smoking cues) and then smoking. Whereas we did find statistically significant interactions of smoking deprivation with smoking cues and with renewed smoking, there was only weak confirmation of a priori predictions of motivational effects of smoking cues or of smoking. We conclude that smoking dependence may not affect the acoustic startle response itself; modulation seems to occur, but only after experience with the test situation. Discussed were possible mechanisms of this modulation in both humans and animals and further application of the startle response for providing interdisciplinary assessments of the motivational effects of nicotine withdrawal.

The influence of low blood pressure and baroreceptor activity on pain responses.

The influence of baroreceptor modulation on pain perception has been extensively studied in normal and hypertensive subjects, but not in hypotensive subjects. The present experiment was performed to verify the following hypotheses: 1. Hypotensive subjects exhibit an increased pain response following baroreceptor activation compared to normals; 2. unlike the hypotensives, normal subjects, with normal baroreceptor reflexes, would learn to choose more often the baroreceptor activation condition compared to the opposite condition, during painful stimulation; 3. sensory and pain thresholds are correlated with blood pressure. The subjects (39 men), divided according to low and normal blood-pressure groups, participated in an experiment in which electrically-induced pain ratings and pain-evoked potentials were measured. Baroreceptor manipulation was performed by means of the PRES procedure. Whereas hypotensive subjects did not perceive any pain difference between the two baroreceptor conditions, activation and inhibition, normotensive men were able to perceive the baroreceptor activation condition as less painful. Similarly to subjective ratings, pain-evoked potentials of the low blood-pressure group showed a reversed trend compared to normals: larger somatosensory evoked potentials (N150-P260) to the baroreceptor activation condition and the opposite to the baroreceptor deactivation condition. Furthermore, results showed a negative correlation between diastolic blood pressure and sensory perception threshold, and a positive correlation between systolic pressure and pain threshold. Contrary to expectations, the rate of choice of baroreceptor conditions during painful stimulation did not show, in either group, any preference for baroreceptor activation.

The Inventory of Drinking Situations (IDS) in current drinkers with different degrees of alcohol problems.

The Inventory of Drinking Situations (IDS) is a questionnaire developed to characterize the situations where alcoholics in treatment drank excessively. The purpose of the present study was to extend the understanding of this instrument as a research and diagnostic tool by applying it to drinking situations in individuals who have never been diagnosed as alcoholics, but who may have problems due to alcohol. Seventy-three current drinkers (32.1 +/- 9.98 years) were examined with a version of the IDS suitable for nonalcoholic individuals. Using the CAGE test we categorized the subjects in five groups according to their score. Correlational analysis revealed that the IDS subscale scores increased significantly with the severity of drinking problems. The CAGE score, the factor-derived scale Negative Situations, being male, and a preference for drinking alone were also correlated with the amount of alcohol consumed, while age was correlated with none of the variables of interest. To facilitate the analysis of the profiles of drinking situations, the IDS subscales underwent a factor analysis that rendered two factor-derived scales, suggesting that drinking occurs both in positive and in negative situations. In persons with more alcohol problems, according to their high CAGE scores, there was more drinking in negative situations that in positive ones. Accordingly, we confirmed that the profiles of drinking situations seen in problem drinkers indicated that situations related to negative emotions are more important determinants to drink. Implications of a shift from drinking in positive to drinking in negative emotional situations are discussed. We further substantiated the value of this test instrument for studies on drinking situations and for studies in nonalcoholic individuals.

Detection of the erect position in the freely-moving human: sensor characteristics, reliability, and validity.

The present report systematically examined a means to electronically detect the erect position in the human in the natural setting. The detector was based on pressure changes in a glycerin filled tube attached to a subject's leg, and it unobtrusively and continuously measured the relative vertical distance between the hip and leg. Initial experiments established the reliability of the sensor system as a function of 1. different sizes of the tubing, 2. different amounts of air in the glycerin and 3. different ambient temperatures (6 degrees-32 degrees C). Then, in a laboratory study of normal adults, the detector was seen to discriminate sitting from standing and (when activity data were included) these two behaviors, in turn, from walking. The detector also accounted for significant differences in HR seen in the standing, as opposed to the sitting, position. In addition, when subjects carried the detector during their daily activities and provided information about their activities using an experience sampling procedure, sitting was discriminated from standing and walking with acceptable diagnostic characteristics. Thus, sitting was detected with a sensitivity of 86.1% (correct detection of all occasions when sitting actually occurred). a positive predictive value of 92.6% (occasions that the detector was right when it indicated sitting), and a negative predictive value of 80.7% (occasions that the detector was right when it indicated sitting). Finally, we demonstrated in two additional ways the direct benefit of our detector in behavioral studies in the natural environment. First, with the detector, we could confirm that a subject had performed simple activities and errands while not under close supervision. Second, cigarette smoking in the natural environment was shown to increase HR, but only when the subjects were sitting. It was concluded that our detector can be effectively applied to the identification of the sitting vs. the erect position in humans in the natural setting, and that this information may be necessary to interpret behavioral and physiological effects seen in such subjects.

Preferences for tastes paired with a nicotine antagonist in rats chronically treated with nicotine.

The present report addressed the hypothesis that withdrawal from chronic nicotine treatment activates the same motivational processes as withdrawal from chronic opiate treatment. Conditioning produced by the nicotine antagonist mecamylamine in nicotine-treated animals was studied and compared to the well-known potentiation by opiate treatment of the aversive conditioning produced by the opiate antagonist naloxone. A sensitive two-flavor, three-trial, taste conditioning procedure was used and it was found that chronic treatment using Alzet minipumps for 1 month with nicotine (8 or 16 mg/kg/day) potentiated the ability of mecamylamine to produce taste conditioning. Thus, in nicotine-placebo control animals, only 1.0 mg/kg mecamylamine (s.c.) produced significant conditioning, whereas in nicotine-treated animals 0.5 and 1.0 mg/kg mecamylamine was effective. However, in contrast to chronic opiate treatment, which increases the aversive effect of an opiate antagonist (as confirmed here using treatment for one month with 0.25 mg/kg/day fentanyl and taste conditioning with 0.1 mg/kg naloxone, s.c.), the nicotine treatment changed the valence of the mecamylamine conditioning. The nicotine-naive animals avoided the mecamylamine-paired flavor, whereas the nicotine-exposed subjects preferred it. These findings indicated that there may be important differences between nicotine and opiate withdrawal. Not all effects of nicotine withdrawal in models of addiction can be assumed to be negatively motivating.

Smoking produces a smaller increase in heart rate in the natural smoking environment than in the laboratory.

We tested whether the physiological effects of smoking a cigarette under standard conditions in a laboratory are similar to those seen in a room at home. On two separate test days ten healthy smokers were prepared with a small physiological recorder and were then requested to carry out a protocol requiring them to smoke one of their cigarettes in their usual way either (1) in the laboratory where they had never smoked previously, or (2) at home, alone in a quiet room where they regularly smoke. The experiment which counterbalanced the order of testing showed that in both test situations smoking produced a clear increase in heart rate (HR) and in skin conductance (SC); however, when testing was carried out in the home environment the increase in the HR was significantly less than in the laboratory. No significant differences were found for the baseline HR values in the two environments and there were no significant situational effects in the SC data. It was concluded that under conditions of normal smoking, data on the physiological effects of a cigarette in the laboratory may not be fully generalizable to those seen in the natural smoking situation. Several possible mechanisms of this situationally-specific effect of smoking were discussed.

Paced smoking in the laboratory and in the natural smoking setting: differential situation-specific effects in light and heavy smokers.

The present study examined the situation-specific effects of smoking using a paced regimen of smoking to control the smoke intake. The subjects were first required to sham smoke and then actually smoke one of their cigarettes in two different test contexts: 1) in the laboratory where they had never previously smoked and 2) at home, alone in a quiet room where they regularly smoke. Light (< 10 cigarettes/day) and heavy smokers (> 15 cigarettes/day) were studied to test for a possible effect of the paced regimen itself. In the light smokers, smoking produced a larger increase in heart rate (HR) in the laboratory than in the natural smoking environment; however, in the heavy smokers the smoking had a larger effect in the normal smoking environment than in the laboratory. There were no significant group or test situation differences for baseline HR, skin conductance and finger temperature. The groups also did not differ in the intensity of drawing on the cigarette or inhaling, as indicated by a puff sensor and a respiratory belt, respectively. It was concluded that differences between the effects of a cigarette in a laboratory setting and in a natural smoking environment may reflect pharmacodynamic effects of smoking that are modified by the subjects' prior experience with smoking. The data are discussed with regard to conditioned tolerance to the effect of smoking.

Excessive drinking situations in German alcoholics: replication of a three-factor model used for North Americans.

German alcoholics were examined for a profile of drinking situations which was found recently in North American alcoholics. A mixed sample of alcoholics (N = 336) receiving in-patient rehabilitation treatment for alcoholism was administered a validated translation of the English version of Annis's Inventory of Drinking Situations (IDS). Analysis of the 100 items in the questionnaire, using principal component methods and varimax rotation, revealed the same three factorial scales seen in the previous study in North American alcoholics (Cannon et al. (1990) Addictive Behaviour 15, 265-269). Drinking was most likely to take place in situations (1) of negative states, (2) of positive states, and (3) where personal control was tested. Although there are large differences in the level and social acceptability of drinking between Central Europe and English-speaking countries, the present data confirm the cross-cultural validity of basic determinants of drinking.

Loss of tolerance to morphine after a change in route of administration: control of within-session tolerance by interoceptive conditioned stimuli.

Tolerance to morphine analgesia (tail-immersion test) was examined after manipulation of two aspects of a tolerance test: 1) the route of drug administration and 2) the time interval between the test dosing and the tolerance test. The intravenous (IV) and intraperitoneal (IP) routes were used, together with a novel test for tolerance in which the test morphine was infused IV just 2 min before measuring the opiate effect. The first experiment validated this test as an assay for tolerance by examining the log dose-response (LDR) curve changes produced by daily IP injection with 0, 20 or 200 mg/kg morphine; the IV test confirmed the expected parallel shift to the right and flattening of the LDR curve. In the second experiment, all rats of two groups were injected once daily for 3 weeks with 20 mg/kg morphine and with saline except that one group received the morphine IV (and saline IP), the other morphine IP (saline IV). The results indicated route-specific tolerance. On a test using 20 mg/kg given IV morphine, tolerance was significantly greater in rats treated with IV morphine than in those treated IP. However, a larger effect on tolerance was produced by a pretest application of 5 mg/kg morphine 30 min before the actual tolerance test. This manipulation was designed to "prime" short-term, adaptive processes hypothesized to occur within a normal tolerance test session as morphine is taking effect. The tolerance on the test increased (equivalent to 2 to 3 fold shift in the LDR curve) when the pretest morphine was given with the same route as the chronic morphine, regardless of treatment group. It was concluded that opiate tolerance may be modulated by conditioned stimuli produced by morphine acting through different routes. These interoceptive cues appear to modulate rapidly acquired and short-lived adaptive processes taking place within a given test session.