Expression of leukocyte integrins and tissue factor in mononuclear phagocytes

Histocompatible Fischer 344 and Lewis rats have been shown to differ on a wide variety of behavioral, chemical, and molecular measures. This investigation aimed to clarify strain differences in unconditioned motor behavior with respect to the amount and patterns of movements. Twenty female Fischer 344, Lewis, and Sprague-Dawley were tested in the Behavioral Pattern Monitor for 30 min. The locomotor activity and movement patterns, quantified by counts of photobeam breaks and the spatial scaling exponent, d, were assessed. The level of locomotor activity did not differ significantly between Fischer, Lewis, and Sprague-Dawley rats. In contrast, movement patterns differed significantly between the strains. Specifically, Sprague-Dawley rats exhibited significantly more straight movements than both Fischer and Lewis rats. Moreover, Lewis rats showed significantly more straight movements compared to Fischer rats during the first 10 min in the enclosures. Differences in movement patterns across strains may provide an important behavioral variable to further explore the genetic and developmental aspects of behavior.     

The suppressive effects of sucrose and cocaine, but not lithium chloride, are greater in Lewis than in Fischer rats: Evidence for the reward comparison hypothesis.

Rats suppress intake of a saccharin conditioned stimulus (CS) when it is paired with an aversive unconditioned stimulus (UCS), an appetitive UCS, or a drug of abuse such as morphine or cocaine. It is unclear, however, whether the reduction in intake induced by these drugs is mediated by their aversive or their rewarding properties. The present set of experiments addressed this question by comparing the suppressive effects of a known aversive UCS (LiCl), a known reinforcing UCS (sucrose), and a drug of abuse (cocaine) in two strains of rats (i.e., Lewis and Fischer 344 rats) that differ in their preference for rewarding stimuli. The results show that, although both strains readily acquired a LiCl-induced conditioned taste aversion (CTA), the suppressive effects of sucrose and cocaine were robust in the drug-preferring Lewis rats and absent in the Fischer rats. These data argue against a CTA account and in favor of the reward comparison hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of isolation rearing on startle reactivity, habituation, and prepulse inhibition in male Lewis, Sprague-Dawley, and Fischer F344 rats

This study compared the interaction of strain with isolation rearing on startle reactivity, habituation, and prepulse inhibition (PPI) in male Lewis, Sprague-Dawley, and Fischer F344 rats tested as adults. Lewis and Fischer rats exhibited lower startle reactivity than Sprague-Dawley rats. Lewis rats displayed more rapid habituation than the other strains. Most important, isolation rearing produced deficits in PPI in both Sprague-Dawley and Fischer rats but had no effect in Lewis rats. By contrast, isolation rearing had no effect on startle reactivity or habituation. In a separate study, 0.5 mg/kg apomorphine disrupted PPI in Fischer but not in Lewis rats. Thus, PPI in Lewis rats is relatively unaffected by either a pharmacological or a developmental manipulation, both of which disrupt PPI in Sprague-Dawley and Fischer F344 rats.     

Ondansetron and Delta-9-Tetrahydrocannabinol Interfere With the Establishment of Lithium-Induced Conditioned Taste Avoidance in the House Musk Shrew (Suncus murinus).

Considerable evidence suggests that rats can learn to avoid a taste in the absence of nausea. The current experiments evaluated the potential of the antiemetic agents, ondansetron (OND) and delta-9-tetrahydrocannabinol (THC), to interfere with lithium chloride (LiCl)-induced taste avoidance in the house musk shrew, Suncus murinus, an insectivore that, unlike rats, is capable of vomiting. At a dose that did not modify saccharin (Experiment 1) or sucrose (Experiment 2) intake, OND prevented the establishment of LiCl-induced taste avoidance in the shrew. A low dose of THC (1 mg/kg), which did not modify sucrose intake during conditioning, also prevented the establishment of LiCl-induced taste avoidance in the shrew. Higher doses of THC were also effective, but they also suppressed sucrose consumption during conditioning. These results suggest that nausea is a necessary component of the unconditioned stimulus for the establishment of conditioned taste avoidance in the shrew, unlike the rat, which does not vomit when injected with a toxin. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned taste and taste-potentiated odor aversions in the Syracuse high- and low-avoidance (SHA/Bru and SLA/Bru) strains of rats (Rattus norvegicus).

SHA/Bru and SLA/Bru rats were selectively bred for good and poor active-avoidance learning. However, SLA/Bru animals are superior to SHA/Bru rats in conditioned suppression and passive avoidance learning. In this experiment, saccharin taste and almond odor were the components of a compound CS (flavor) in an illness-induced aversive conditioning paradigm. SLA/Bru rats (n?=?17) showed stronger conditioned flavor, taste, and odor aversion than did SHA/Bru animals (n?=?18). Unselected Long-Evans rats (n?=?18) were intermediate between the selected strains. SLA/Bru and Long-Evans rats showed taste-potentiated odor aversion in this experiment, whereas SHA/Bru animals did not. The results provide evidence that genetic factors, as exemplified by the different strains, are importantly involved in the mechanisms underlying interoceptive and exteroceptive aversive conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The painlike effect of gallamine and naloxone differs from sickness induced by lithium chloride.

In 3 experiments with 60 male Sprague-Dawley rats, LiCl (31.8 mg/kg, ip) produced stronger taste aversions than gallamine triethiodide (10 mg/kg) or naloxone HCl (2.5 or 20 mg/kg), but gallamine and naloxone each produced stronger place aversions than lithium. Findings support the distinction between 2 kinds of drug-induced aversive effects, with different associative properties. One effect, called sickness, is more associable with taste than with place cues; the 2nd effect is, like pain, more associable with place than with taste. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strain differences in maintenance of cocaine self-administration and their relationship to novelty activity responses.

The authors previously demonstrated that Fischer 344 (F344) and Lewis inbred rats differ in acquisition of cocaine self-administration. Other studies show that acquisition and maintenance of drug self-administration are predicted by locomotor activity in a novel environment among outbred Sprague-Dawley rats. The present study was designed to determine whether this relationship extended to F344 and Lewis rats. In Experiment 1, F344, Lewis, and Sprague-Dawley rats were trained to self-administer cocaine and tested with several doses under fixed- and progressive-ratio schedules of reinforcement. Self-administered infusions and ineffective active lever presses--those emitted during infusion and time-out periods--were assessed. In Experiment 2, separate sets of rats of each strain were examined for locomotor responses (distance traveled and center time) under novelty conditions. Results show that F344 rats self-administer more cocaine than Lewis or Sprague-Dawley rats under both schedules and emit more ineffective lever presses--a possible measure of craving. Strain comparisons of locomotor responses suggest that center time, not activity, relates to self-administration behavior. Maintenance studies of cocaine self-administration rather than acquisition may better reflect vulnerability to addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rat strain differences in flap tolerance to ischemia

The rat epigastric island flap model is commonly used to explore ischemia-related phenomena. We sought to evaluate strain differences in tolerance to ischemia using two commonly used rat strains: Sprague-Dawley and Lewis. Epigastric flaps (3 x 6 cm) based on the superficial epigastric artery and vein were raised bilaterally in each rat (2 flaps/rat). Ischemia was induced for 10,12,14, or 16 hours by placing temporary occlusion clamps on each vessel of the vascular pedicle. Surviving flap areas were assessed planimetrically after 7 days. The average area of surviving flap tissue was greater in the Lewis rats for all ischemia times; this achieved significance for 12 hours and 14 hours of ischemia (P < 0.005). These findings indicate that comparisons among studies on rat flap ischemia must take into account the particular strain used. Furthermore, these findings suggest an inherent capacity of Lewis rat tissue to withstand ischemia better than tissue of the Sprague-Dawley rat strain.     

Taste avoidance, but not aversion, learning in rats lacking gustatory cortex.

Control rats rapidly learned to avoid drinking either a sucrose solution (Exp 1) or an NaCl solution (Exp 2) when the taste was paired with illness. These rats also produced aversive reactivity to each of these solutions in a taste reactivity test. Rats that lacked gustatory cortex (GC) learned to avoid drinking sucrose and NaCl, albeit at a slower rate than control rats. GC rats failed to display aversive reactivity to these tastes. The GC rats did show normal aversive reactivity to a strong quinine HCl solution during additional tests. It is suggested that the avoidance developed by GC rats did not entail a palatability shift of the conditional stimulus as it did in control rats. This altered learning strategy may account for the consistent learning deficits found in GC rats trained to avoid tastes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of an aversive Pavlovian conditional stimulus with aversively and appetitively motivated operants in rats.

Reports results of 5 experiments with a total of 168 male albino Sprague-Dawley rats. Presentation of an aversive CS produced an acceleration of free-operant Sidman shock-avoidance responding only if the CS had been paried with a relatively weak-shock UCS. Stimuli paired with a relatively strong UCS produced suppression of avoidance responding. With appropriate shock intensities, both suppression and acceleration were obtained. Responses of controls showed that this effect was not due to interactions between the operant response and UCS. In a within-S experiment, the same aversive CS produced suppression of an appetitive response (CER) and acceleration of avoidance. However, a CS which had produced avoidance acceleration did not suppress an appetitive operant. (23 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the lateral parabrachial nucleus block the aversive motivational effects of both morphine and morphine withdrawal but spare morphine's discrimination properties.

This study examined if the aversive properties of morphine, the aversive properties of morphine withdrawal, and the discriminative properties of morphine are mediated by common neurobiological substrates. Lesions of the lateral parabrachial nucleus, which blocked the aversive properties of morphine in the conditioned taste aversion paradigm, also blocked the acquisition of conditioned place aversions to environments paired with the aversive properties of morphine withdrawal in morphine-dependent rats. When morphine and saline were used as cues in a discrimination task, however, both sham-operated and lesioned rats were able to solve the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

LSD produces place preference and flavor avoidance but does not produce flavor aversion in rats.

The hedonic properties of lysergic acid diethylamide (LSD) were assessed using the place conditioning, taste reactivity, and taste avoidance tests. LSD produced a conditioned place preference, but only at the highest dose tested (0.2 mg/kg). A single preexposure to the conditioning chamber (latent inhibition) prevented the establishment of a place preference. When paired with sucrose, doses of 0.05 to 0.2 mg/kg of LSD produced taste avoidance, but no dose of LSD produced an aversion to the taste as assessed by the taste reactivity test. These results suggest that LSD, like other rewarding drugs, produces taste avoidance by a mechanism other than that produced by emetic drugs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pavlovian extinction in rats during avoidance response prevention.

Attempted to determine whether extinction of the aversive properties of a CS occurs during avoidance response prevention. 48 naive male albino Sprague-Dawley rats served as Ss. The CS remained somewhat aversive even after 5 5-min unreinforced presentations during response prevention, but it was significantly less aversive for Ss exposed to it without reinforcement than for nonblocked Ss or for blocked Ss given unreinforced exposures to the shock compartment in the absence of a CS. This finding supports analyses which assign a contributory role to Pavlovian extinction of CS aversiveness in facilitating avoidance extinction by response prevention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the lateral parabrachial nucleus block the aversive motivational effects of both morphine and morphine withdrawal but spare morphine's discriminative properties

This study examined if the aversive properties of morphine, the aversive properties of morphine withdrawal, and the discriminative properties of morphine are mediated by common neurobiological substrates. Lesions of the lateral parabrachial nucleus, which blocked the aversive properties of morphine in the conditioned taste aversion paradigm, also blocked the acquisition of conditioned place aversions to environments paired with the aversive properties of morphine withdrawal in morphine-dependent rats. When morphine and saline were used as cues in a discrimination task, however, both sham-operated and lesioned rats were able to solve the task.     

Sodium depletion enhances salt palatability in rats.

Stereotyped fixed action patterns (FAPs) elicited in rats by oral infusions of taste solutions can be classified as either ingestive or aversive. They reflect the palatability of the taste and can be modified by learning and by the physiological state of the animal. The present 2 experiments, with 5 male Sprague-Dawley rats, demonstrated that when the physiological state of the S was altered by sodium depletion, the pattern of FAPs elicited by oral infusions of 0.5 M NaCl shifted from a mixture of ingestive and aversive components (while sodium replete) to exclusively ingestive ones (while sodium deplete). This shift in taste reactivity occurred the 1st time the Ss were made sodium deplete. A similar shift did not accompany infusions of 0.01 M HCl, a taste solution that also elicited mixed ingestive and aversive FAPs. This result suggests that the shift in response to NaCl was not due to a general change in ingestive bias or to a general taste deficit. On the basis of the change in FAPs, it is concluded that the palatability of highly concentrated salt solutions increases in sodium-deplete rats. Such a shift in salt palatability may be instrumental in directing the appetitive behavior of the animal. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Separation of taste-aversion-prone and taste-aversion-resistant rats through selective breeding: Implications for individual differences in conditionability and aversion-therapy alcoholism treatment.

Reports on the ongoing development of rat strains suitable for studies of biological bases of individual differences in taste aversion (TA) conditionability. Sprague-Dawley-derived rats were selectively bred over 7 generations as strong or weak learners of a TA to saccharin induced by intraperitoneal injections of cyclophosphamide (12.5 or 15 mg/kg). Efficiency of aversion acquisition was a selectable propensity, as indicated by progressively divergent strain separation that attained significance in the 2nd selected generation. Ss were also studied with respect to shock-motivated environmental avoidance (SMEA), but efficiency of SMEA performance was not a selection factor. Results show an unexpected trend across generations indicative of a within-strain reversal of TA and SMEA learning efficiency. Continuation of this reversal in subsequent generations could have important implications for studies of genetic contributions to different learning capacities and for the selection of biologically appropriate noxious stimuli for aversive therapy treatments of various target problems, sush as alcoholism. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

ACTH and ACTH4–20 modification of neophobia and taste aversion responses in the rat.

A series of 6 experiments assessed the effects of ACTH and the ACTH analog ACTH4–20 on drinking in conditioned taste aversion and neophobic situations using a total of 168 male Sprague-Dawley rats as Ss. Both substances delayed the extinction of a conditioned taste aversion established by a single pairing of lithium chloride with milk (Exp I). However, in this situation, the ACTH parent peptide was more potent behaviorally. ACTH supressed milk consumption in Ss with no toxicosis experience (Exp II). This effect was apparently not due to the conditioning of a taste aversion (Exp III) with ACTH serving as a weak aversive UCS. Exogenous ACTH (Exp IV) or ACTH4–20 (Exp V) did not enhance neophobia; however, repeated injections of ACTH suppressed drinking. This ACTH suppression was related to the familiarity/novelty of the substance being consumed. The neophobic response to milk was not accompanied by pituitary-adrenal activation (Exp VI). Both neophobic and conditioned taste aversion situations appear to be useful for assessing peptide effects on consummatory behavior. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differences in kindling development in seven outbred and inbred rat strains

The kindling phenomenon, i.e., the progressive development of focal and secondarily generalized seizures upon repeated electrical stimulation of a limbic brain region, occurs in various species, but with marked differences in kindling rate between species and also within the same species. In rats, differences in kindling rates have been reported within the same strain and between different strains, and both genetic and environmental influences are thought to be involved in this variability. In most studies on kindling in rats, outbred strains such as Sprague-Dawley have been used. In the present study, we compared rates of amygdala kindling development in two outbred (Sprague-Dawley, Wistar) and five inbred (Lewis, Fischer 344, ACI, Wistar-Kyoto, Brown Norway) rat strains, including several strains which have not been kindled before. We were particularly interested which parts of the stepwise progression of kindling differ among these strains. Furthermore, the sensitivity of the basolateral amygdala to electrical stimulation was determined before and after kindling. Once daily electrical stimulation of the basolateral amygdala resulted in marked interstrain differences in kindling rates, with Sprague-Dawley and Brown-Norway rats exhibiting the lowest number of stimulations to reach fully kindled (stage 5) seizures, and Lewis rats showing the highest number of the 7 strains. In contrast to the significant differences in number of stimulations to reach the fully kindled state, total (cumulative) afterdischarge duration (ADD) to reach stage 5 did not significantly differ among strains, substantiating that cumulative AD is the principal factor in the acquisition of kindled seizures. Marked differences in ADD of a stage 5 seizure were obtained between strains, with strains kindling rapidly exhibiting longer ADD than strains kindling slowly. Postkindling afterdischarge threshold (ADT) varied significantly among strains, but only 3 of the 7 strains showed a decrease of ADT compared to prekindling values. When the stepwise progression of kindling was evaluated, pronounced interstrain differences were determined in the time spent in the initial phase of kindling, i.e., stage 1 seizures, both in terms of stimulations and cumulative ADD, indicating that variations in kindling rates were predominantly due to the time needed to progress from stage 1 to subsequent stages of the kindling process. The data seem to indicate that inbred rat strains offer an interesting resource for dissecting the underlying genetic basis for phenotypic differences in epileptogenesis as induced by kindling, although the high variability of kindling rates seen within some inbred strains weakens this possibility.     

Strain differences in avoidance conditioning as a function of the classical CS-US contingency.

Examined rates of shuttle box avoidance responding in 3 strains of rats as a function of classical and instrumental contingencies in 2 experiments. Ss were a total of 126 female albino Fischer, Lewis, and Long-Evans rats. In Exp I, during classical conditioned-stimulus-unconditioned-stimulus (CS-UCS) pairings in the absence of an avoidance contingency, there were large differences between the 3 strains in rates of anticipatory responding to the CS. The same pattern of differences was observed in Exp II when the avoidance contingency was added. None of the instrumental contingencies of CS termination, UCS termination, or the avoidance contingency differentially affected the strains. Classically elicited anticipatory responses and their compatibility with the required avoidance response were viewed as central factors in both the acquisition and maintenance of skeletal avoidance responses. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The pulsatile characteristics of hypothalamo-pituitary-adrenal activity in female Lewis and Fischer 344 rats and its relationship to differential stress responses

The dynamic patterns of basal and stimulated hypothalamo-pituitary-adrenal (HPA) activity of freely moving female Lewis and Fischer 344 rats were compared using an automated blood-sampling system. Both strains showed pulsatile corticosterone release throughout the 24 h cycle. Lewis rats showed clear circadian variation in both pulse frequency (8.4 +/- 0.4 pulses between 1700-2300 h vs. 5.3 +/- 0.8 pulses between 0500-1100 h; P < 0.05) and height (198 +/- 27 ng/ml between 1700-2300 h vs. 107 +/- 14 ng/ml between 0500-1100 h; P < 0.05). Fischer rats exhibited pulses of similar frequency and height to those in Lewis rats during the evening, but showed no circadian variation, resulting in higher mean daily corticosterone concentrations. Although both strains showed behavioral and HPA responses to white noise stress (10 min; 114 dB), Fischer rats showed much greater increases in total activity, grooming, and rearings, and two important differences in the corticosterone responses were observed. First, in Lewis rats a clear relationship existed between basal and stimulated HPA activities, in that a significant response was seen only when the stress coincided with the rising (secretory active) phase of a basal pulse. Noise stress coinciding with a falling (nonsecretory) phase elicited no significant response. In contrast, Fischer rats showed similar responses regardless of the underlying pulse phase. Second, after the peak response at 20 min (Lewis, 237 +/- 67 ng/ml; Fischer, 390 +/- 57 ng/ml), corticosterone levels fell rapidly in Lewis rats, but remained maximally elevated for 20 min in Fischer rats, resulting in a significantly greater integrated response. The corticosterone response to i.v. CRF was unaffected by pulse phase in both strains, suggesting that a suprapituitary mechanism mediates the phase-dependent response to stress in the Lewis strain. CRF-induced corticosterone levels rose more rapidly in Fischer rats, peaking at 10 min (473 +/- 95 ng/ml) compared with 30 min (390 +/- 75 ng/ml) in Lewis rats, suggesting greater pituitary sensitivity in this strain. Thus, differences in both central and pituitary control of the HPA axis contribute to the strain difference in stress responsiveness between female Lewis and Fischer rats.