Absence of oxidative stress following paradoxical sleep deprivation in rats

With an aim of creating new, high affinity dopaminergic ligands, six different 3- and 4-substituted 1-[2-[5-(1H-benzimidazole-2-thione)] ethyl]piperidines and nine related heterocyclic congeners were synthesized and evaluated for in vitro binding affinity at D1 and D2 dopamine receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei were used as a source of the dopamine receptors. Only 4-[bis-(4-fluorophenyl)methylene]-piperidines, compounds 9e, 10d, and 11d, expressed moderate affinity for the D1 receptors, while all other compounds were inactive competitors of [3H]SCH 23390. Compounds 9c, 9d, 10c, 11a, and 11c were inactive in the D2 receptor binding assay, as well. Derivatives of 4-phenylpiperidine (9-11b) and 3-phenylpiperidine (10a) expressed a moderate to low affinity for the D2 receptors. However, racemic (+/-)-1-[2-[5-(1H-benzimidazole-2-thione)] ethyl]-3-phenylpiperidine 9a and its enantiomer (+)-9a behaved as selective, high affinity D2 receptor ligands, the latter being some four times more active than the racemate.     

Posttraining paradoxical sleep in rats is increased after spatial learning in the Morris water maze.

The role of posttraining paradoxical sleep (PS) in spatial or nonspatial learning in the Morris water maze was evaluated. Sprague-Dawley rats were given a 12-trial training session in either the hidden or the visible platform versions of the task. Subgroups then underwent paradoxical sleep deprivation (PSD) beginning at different times after training. Rats with PSD imposed from 14 hr after spatial training had poorer retest scores than any other group. Other rats, implanted with electrodes to permit continuous recording of sleep electroencephalography, were found to undergo a prolonged period of elevated PS after spatial training. By contrast, rats trained in the nonspatial version of the water maze task did not show retention deficits after PSD or elevated PS after training. These results support a role for PS in spatial, but not nonspatial, learning in the Morris water maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear conditioning increases NREM sleep.

To understand the role that sleep may play in memory storage, the authors investigated how fear conditioning affects sleep-wake states by performing electroencephalographic (EEG) and electromyographic recordings of C57BL/6J mice receiving fear conditioning, exposure to conditioning stimuli, or immediate shock treatment. This experimental design allowed us to examine the effects of associative learning, presentation of the conditioning stimuli, and presentation of the unconditioned stimuli on sleep-wake states. During the 24 hr after training, fear-conditioned mice had approximately 1 hr more of nonrapid-eye-movement (NREM) sleep and less wakefulness than mice receiving exposure to conditioning stimuli or immediate shock treatment. Mice receiving conditioning stimuli had more delta power during NREM sleep, whereas mice receiving fear conditioning had less theta power during rapid-eye-movement sleep. These results demonstrate that a single trial of fear conditioning alters sleep-wake states and EEG oscillations over a 24-hr period, supporting the idea that sleep is modified by experience and that such changes in sleep-wake states and EEG oscillations may play a role in memory consolidation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Appetitive and aversive conditioning in thiamine-deficient rats.

Reports results of 3 experiments with albino male (n = 65) and female (n = 38) thiamine-deficient rats. 4 pairings of saccharin drinking with thiamine injection increased intake of saccharin whether tested before or after a further injection of thiamine. 2 injections of oxythiamine paired with saccharin drinking almost completely suppressed saccharin intake 1 wk. later, whether the diet during the week was thiamine enriched or thiamine free. Pairing thiamine injections with one flavor and oxythiamine injections with another in the same Ss produced a preference for the thiamine-paired flavor, but intake of both flavors was lowered in comparison with a control group. (21 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential conditioning and contrast effects in rats.

Considers previous research, using a differential conditioning procedure to examine contrast effects in the runway, inadequate due to the operation of a ceiling effect and/or a decision-time problem. A special procedure (delay of reward and massing trials) was used to solve these problems in an experiment with 40 male Holtzman albino rats. Results reveal reliable positive and negative contrast effects. Data support the conclusions, that (a) it is reasonable to seek a common explanation of behavioral contrast (operant) and incentive contrast (runway) data; (b) perceptual theories of contrast, predicting both positive and negative contrast, are to be preferred over theories designed to predict only negative contrast; and (c) the type of response, and extraneous variables which affect it, needs to be carefully considered in dealing with reward manipulations. (21 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The paradoxical hedonic valence of acute ethanol withdrawal (hangover) states in rats: place and taste conditioning

We describe the synthesis and pharmacological properties of two series of analogues: one which consists of three peptides having L-1-naphthylalanine in position 3 and the second composed of analogues substituted in position 3 with L-2-naphthylalanine. All peptides were tested in bioassays for pressor and antidiuretic activities. We also checked the uterotonic activity in vitro. We observed that the activity of counterparts in both series is, in two cases, strikingly different. One of the new analogues, [(L-2-Nal)3,(D-Arg)8]VP is among the most potent antagonists of the vasopressor response to AVP. Moreover, it is the first potent V1 antagonist devoid of antiuterotonic activity. This analogue was designed without modification of position 1, which was previously thought to be essential for substantial pressor antagonism. Two other peptides, [Mpa1;(L-2-Nal)3;(D-Arg)8]VP and [Mpa1,(L-1-Nal)3,D-Arg)8]VP, are highly potent V2 agonists. The second analogue is highly selective. With the exception of [(L-2-Nal)3]AVP, which showed weak antioxytocic activity, (L-Nal)3 modification resulted in the almost complete removal of interaction of our analogues with oxytocic receptors in vitro. Our results suggest that position 3 in AVP and its analogues is important not only for binding and recognition as previously though, but also for pressor, antidiuretic and uterotonic activities. We also assume that the hindering effect caused by bulky naphthyl moiety has a significant impact on the bioactive conformations of molecules which contain Nal residue, and can thus influence their interaction with V1, V2 and oxytocic receptors.     

Hyperoxia increases paradoxical sleep rhythm in the pontine cat

Pontine cat is an ectothermic preparation, whose central temperature can artificially be lowered from 36 degrees C to 26 degrees C; this gradual hypothermia is accompanied by a dramatic increase in paradoxical sleep (PS). Two main hypotheses might explain this result: executive systems of PS might be switched on gradually by cold-sensitive thermodetectors, whereas inhibitory monoaminergic mechanisms appear to be warm-sensitive. On the other hand, energy saving mechanisms peculiar to hypothermia might promote PS appearance. Indeed, in normal animals, PS is selectively suppressed both by hyperthermia and hypoxia. The inhibitory effect of hypoxia might explain why hypothermia, which protects the brain against hypoxic alterations, might facilitate PS. If this last hypothesis is correct, the putative increase in cerebral oxygen supply might increase PS. For this reason, we submitted eight pontine carotid-deafferented cats, kept at the same central temperature (34 +/- 0.5 degrees C: temperature clamp) to periodic hyperoxia (PaO2 = 58 +/- 7 kPa) or room air (PaO2 = 17 +/- 2 kPa) alternatively during 4- or 12-h periods. Hyperoxia induced an 85% increase in PS, mainly due to an increase in PS rhythm (PS cycle duration was 65 +/- 4 min in normoxia and 45 +/- 4 min in hyperoxia, p<0.0001). In five animals, after hyperoxia, PS cycle returned gradually back to control values in 4 to 12 h. These findings show that PS is exquisitely sensitive to conditions that impair oxidative metabolism. The role of cholinergic executive PS systems as putative metabolic-sensitive neurons remains to be established.     

Some parameters affecting shuttle-box avoidance responding with rats receiving serially presented conditioned stimuli.

Gave 48 male Blue Spruce rats shuttle-box training with serial or nonserial CS procedures. The serial CS condition (S1/S1S2), which involved a single stimulus for the 1st 1/2 of a 16-sec CS-UCS interval and 2 stimuli for the latter 1/2, produced shorter avoidance latencies and more avoidance responses when compared with a serial condition (S1/S2), in which the latter 1/2 of the interval involved only 1 stimulus. Both serial conditions resulted in longer avoidance latencies when compared to nonserial conditions. Exp. II with 144 Ss demonstrated that the above latency differences could be eliminated with shorter CS-UCS intervals, and Exp. III with 72 Ss suggested that avoidance-latency differences obtained at longer CS-UCS intervals were independent of the CS duration ratio between serial components. These and other findings were predicted from a generalization-decrement hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning-induced plasticity in the medial geniculate nucleus is expressed during paradoxical sleep.

Fear conditioning to an acoustic stimulus produces increases in tone-evoked discharges of neurons in the medial division of the medial geniculate nucleus (MG). This study examined the responses of MG neurons to a conditioned tone presented in paradoxical sleep (PS). After 1 session of habituation to a tone, awake rats underwent conditioning in 3 sessions during which the tone was used as the CS preceding a footshock. Control rats received unpaired presentations of tone and shock. The same tone, which never awakened the animal, was presented during PS following each daily session. Responses of MG neurons to the tone in PS were increased after conditioning. This enhancement was as large as that in waking and was manifested earlier after tone onset than in waking. No change appeared after pseudoconditioning. These results demonstrate that associatively induced plasticity in the MG can be expressed during PS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Use of paradoxical intention in a behavioral program for sleep onset insomnia.

Sleep onset insomnia seems often to be based on performance anxiety associated with a client's fears of being able to fall asleep; in some cases, a therapeutic program might actually exacerbate this performance anxiety by focusing on the client's efforts to voluntarily control the sleep onset process. Five Ss aged 23–41 yrs and experiencing sleep onset difficulty unusually resistant to a conventional behavioral program for this problem (i.e., deep muscle relaxation and systematic desensitization), were exposed to paradoxical intention suggestions requiring that they try to remain awake as long as possible, rather than attempt to fall asleep. A rapid reduction of sleep onset latency occurred following the shift from the conventional program to the paradoxical intention instructions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Escape conditioning in wild and domestic Norway rats.

Tested 16 female wild (lab-reared) and 16 female domestic Norway rats for acquisition of a conditioned escape response. To escape from an aversive stimulus (air blasts) Ss were required to open 1 of 8 doors (simulated burrow entrances) on the presence of a visual cue. Stocks did not differ in the rate of conditioning. Wild Ss exhibited significantly shorter latencies for ambulation and escape than domestic Ss. Removal and reinstatement of the visual cue following acquisition confirmed that the Ss used the cue for orientation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Injection of ACTH induces recovery from shuttle-box avoidance deficits in rats with amygdaloid lesions.

In an experiment with 27 female Wistar rats, amygdalectomy caused a deficit in the acquisition of a shuttle-box conditioned avoidance response and in other aversively motivated tasks, supporting previous findings. Amygdalectomized Ss given ACTH 1 hr. prior to acquisition exhibited no such deficit. Previous evidence relating the amygdaloid complex to the pituitary-adrenal axis is used as a basis for arguing that mobilization of steroid hormones is a necessary component of certain types of fear-motivated responses. (21 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of activity and immobility conditioning upon subsequent heart-rate conditioning in curarized rats.

Assigned 40 female Long-Evans hooded rats to experimental or yoked-control groups receiving activity conditioning in a running wheel or immobility conditioning in a small open field. Following 10 days under these procedures, all Ss were curarized and punished either for the emission of high or low heart rates. The pretraining procedures contributed significantly more to the heart-rate changes observed under curare than did the reinforcement contingencies imposed under this latter condition. Implications are discussed with respect to the specificity of operant cardiovascular conditioning and the general issue of somatocardiovascular relations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contrast effects in escape conditioning of rats.

In Exp I 39 male Holtzman albino rats ran for 20 trials from an alley where they received .2-, .4-, or .8-ma shocks to a goal box where there was no shock. All Ss were then shifted to .4 ma in the alley for 20 trials. Results show that rapid adjustment of running speeds occurred with shifts in amount of escapable shock. More importantly, however, positive and negative contrast occurred. In Exp I an experimental group (n = 10) received .2 ma on half of the trials and .4 ma on the other half, and 2 control groups (n = 10) received either .4 or .2 ma on all trials. Results show that the experimental group escaped faster on .4-ma trials than the .4-ma control group (positive contrast) and escaped more slowly on .2-ma trials than the .2-ma control (negative contrast). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cholecystokinin conditioning in rats: Ontogenetic determinants.

Low doses (0.12–2.0 μg/kg) of cholecystokinin octapeptide (CCK), administered intraperitoneally, support the formation of conditioned odor preference in neonatal and weanling rats. Exposure to a novel odor was paired with CCK injection, and the rats' olfactory choices were assessed 24 hr later. Rats at 5, 11, and 22 days of age preferred the odor previously associated with CCK, compared with vehicle-injected littermates. In contrast, CCK failed to support olfactory conditioning in 28-day-old rats, whether they were (a) weaned and independently housed, (b) residing with the dam and suckling, or (c) fed only milk. Adult rats also did not establish an odor preference with CCK as the unconditioned stimulus. Thus, CCK's changing impact from positive to neutral probably occurs during the rats' 4th postnatal week and may be related to maturational changes occurring during the final stages of weaning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Examination of bilateral eyeblink conditioning in rats.

This experiment monitored eyelid responses bilaterally during delay eyeblink conditioning in rats. Rats were given paired or unpaired training with a tone or light conditioned stimulus (CS) and a unilateral periorbital shock unconditioned stimulus (US). Rats given paired training acquired high levels of conditioned responses (CRs), which occurred in both eyelids. However, acquisition was faster, and the overall percentage of CRs was greater in the eyelid that was ipsilateral to the US. CRs in the eyelid ipsilateral to the US also had shorter onset latencies and larger amplitudes than CRs in the contralateral eyelid. Both eyelids consistently showed high percentages of unconditioned responses (UR) to the US, and the UR amplitude decreased across training sessions in the paired group. The present study demonstrated that CRs occur robustly in both eyelids of rats given eyeblink conditioning, which is similar to previous findings in humans and monkeys. The results also showed that conditioning occurs more prominently in the eyelid that is ipsilateral to the US, which is similar to previous findings in humans, monkeys, dogs, and rabbits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Autonomic and behavioral correlates of appetitive conditioning in rats.

The cardiac responses accompanying conditioned stimulus (CS)-generated (orienting) and unconditioned stimulus (US)-generated appetitively motivated behaviors (P. C. Holland, 1977) were investigated. On the basis of contemporary psychophysiological research, CS-generated responses were predicted to produce bradycardia, and US-generated responses to produce tachycardia. Pairing a 10-s visual CS with food delivery produced conditioned behavioral orienting (rearing) during the initial portion of the CS, followed by magazine approach (US-generated) responses as the CS progressed. CS onset produced a decrease in heart rate, mediated by an increase in parasympathetic stimulation of the heart, which persisted throughout the 10-s CS; no support for a biphasic cardiac response was observed. These data are discussed with respect to other conditioned autonomic responses and their relevance to foraging and food ingestion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired trace and contextual fear conditioning in aged rats.

Trace and contextual fear conditioning were evaluated in adult (3-6 months), early middle-aged (8-12 months), late middle-aged (16-20 months), and aged (24-33 months) Sprague-Dawley rats. After trace conditioning, aged animals exhibited significantly less freezing to the tone conditioned stimulus and training context. Levels of trace-cue and context conditioning were negatively correlated with age (r = -0.56 and -0.59, respectively) and positively correlated with each other (r = +0.52). Aged rats showed robust conditioning in short- and long-delay fear paradigms, suggesting that the trace interval, rather than the use of a long interstimulus interval, is responsible for the aging-related deficits in trace fear conditioning. The authors suggest that these aging-related conditioning deficits furnish useful indices of functional changes within hippocampus or perirhinal cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Variations in intensity, interstimulus interval, and interval between preconditioning CS exposures and conditioning with rats.

Investigated the relationship between preconditioning exposure to a stimulus later employed in conditioning as a CS and suppression of a licking response in the presence of that stimulus, in 2 experiments with a total of 216 male albino Sprague-Dawley rats. In Exp. I, a direct relationship was found between intensity of preconditioning stimulus and magnitude of suppression reduction. There was also evidence for the effects of stimulus intensity during conditioning and the operation of generalization decrement when conditioning and test stimulus intensities were not the same. Exp. II showed that preconditioning CS exposure reduced suppression to the test CS on the 1st test trial, regardless of interval between preconditioning exposures or preexposure and conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Music-induced context preference following cocaine conditioning in rats.

Traditional models of drug-seeking behavior have shown that exposure to associated environmental cues can trigger relapse. These learned associations take place during repeated drug administration, resulting in conditioned reinforcement. Although considerable investigation has occurred regarding simple conditioned stimuli, less is known about complex environmental cues, particularly those that may be salient in human addiction. Recent studies indicate that music can serve as a contextual conditioned stimulus in rats and influence drug-seeking behavior during abstinence. The purpose of the present study was to further assess the effectiveness of music as a conditioned stimulus in rats, to determine rats' preferences for two contrasting pieces of music, and to determine rats' preferences for music versus silence. To this end, we created an apparatus that gave instrumental control of musical choice (Miles Davis vs. Beethoven) to the rats themselves. After determining baseline musical preference, animals were conditioned with cocaine (10 mg/kg) to the music they initially preferred least, with alternating conditioning sessions pairing saline with the music preferred most. The animals were subsequently tested in a drug-free state to determine what effect this conditioning had on musical preference. The results indicate that music serves as an effective contextual conditioned stimulus, significantly increasing both musical preference and locomotor activity after repeated cocaine conditioning. Furthermore, we found that rats initially favor silence over music, but that this preference can be altered as a result of cocaine-paired conditioning. These findings demonstrate that, after repeated association with reward (cocaine), music can engender a conditioned context preference in rats; these findings are consistent with other evidence showing that musical contextual cues can reinstate drug-seeking behavior in rats. (PsycINFO Database Record (c) 2011 APA, all rights reserved)