Selective absorption of radio frequency energy due to collective motion of charged domains: case of lysozyme crystal

The role of the N-methyl-D-aspartate (NMDA) receptors in cocaine conditioning and sensitization of locomotor activity was studied in four groups of Sprague-Dawley rats. A sub-motoric dose of the NMDA antagonist MK-801 (0.1 mg/kg, i.p.) was employed using a novel dual-compartment Pavlovian drug conditioning paradigm. The animals were placed sequentially in two different test environments in which locomotor activity was monitored. In the first compartment, the animals always received a non-drug test for 20 min. Upon completion of this test, the animals received either saline, cocaine (10 mg/kg i.p.), MK-801 or MK-801 plus cocaine depending on group assignment and were then placed immediately into the second compartment and again tested for 20 min. A total of six non-drug and six drug tests were conducted every other day over a 12-day period. Across all drug/saline treatment and post-treatment tests for conditioning, there were no statistical differences in locomotor activity among the saline and drug treatment groups in the non-drug test environment. In the drug/saline associated environment, however, cocaine had a reliable stimulant effect on locomotion when administered alone or in combination with MK-801. Following a 1-day and again after 21-days of withdrawal, all animals were administered a non-drug test for conditioning in which no injections were administered. On both tests, all groups had equivalent activity levels in the non-drug environment. In the drug/saline environment, only the cocaine group of the three drug treatment groups exhibited conditioned hyperlocomotion. Importantly, MK-801 blocked conditioned hyperlocomotion in the combined cocaine+MK-801 group. MK-801 did not alter serum or brain cocaine concentration or the cocaine effects on dopamine metabolism in limbic brain tissue. The co-administration of MK-801 with cocaine, however, blocked the corticosterone release effect of cocaine. Thus, the NMDA receptor site appears critical for cocaine induced conditioning and for corticosterone release.     

Immune function alterations in mice tolerant to delta9-tetrahydrocannabinol: functional and biochemical parameters

The present study examined (1) whether the neostriatum is involved in a drug-induced conditioned locomotor response and; (2) whether this structure participates in the development of behavioral sensitization. Moreover, the present study addressed the question whether the development of behavioral sensitization is necessary for the induction of conditioning. Rats received injections of either apomorphine (2 microg) or vehicle (solution of 0.1% ascorbate/saline) into the dorsal neostriatum daily for 7 days. These treatments were performed immediately prior to (apomorphine-paired group and vehicle group) or 30 min following (apomorphine-unpaired group) 10-min placement in an open field which served as the test environment. After a 3-day drug withdrawal period, the animals were given a 10-min non-drug vehicle test trial in the test environment. Three days later, a drug test with apomorphine was administered to the animals of the paired and unpaired treatment groups; the vehicle group again received an injection of vehicle. The analysis of locomotor activity in the open field (measured as the distance traversed) revealed that locomotor activity in the apomorphine-paired group was higher than in the other groups. There were no indications for behavioral sensitization to intrastriatal apomorphine, since the locomotor response in the apomorphine-paired group did not increase, but rather decreased with daily repeated injections of apomorphine. Furthermore, only the apomorphine-paired animals showed a higher locomotor response when tested after an intrastriatal injection of vehicle in the previously apomorphine-paired environment, which is indicative of a conditioned drug effect. These results suggest that the neostriatum is directly involved in the development of drug-induced conditioning of locomotor behavior but not in the establishment of behavioral sensitization.     

Daily wheel running activity modifies the period of free-running rhythm in rats via intergeniculate leaflet

The period of free-running rhythms (tau) in rats, as measured using a running wheel, is different from that measured using an Automex. The aim of this work was to examine the effects of lesions of the intergeniculate leaflet (IGL) on the tau of these two activity rhythms. When blind rats were transferred from a cage with a running wheel to a cage without a running wheel, the tau lengthened. The tau of the wheel-running activity was associated with the number of wheel revolutions per day. A complete lesion of the IGL lengthened the tau of the wheel-running activity, and caused a reduction in the number of wheel revolutions per day in all rats. In rats housed in cages without a running wheel, locomotor activity was reduced by IGL lesions, although the tau was unaffected. When IGL-lesioned rats were transferred from a cage with a running wheel to a cage without a running wheel, no further change was observed. These results indicate that the tau is modified by the daily activity of wheel-running, but not by general locomotor activity, and that the IGL may be involved in this modification.     

Investigation of topical ciprofloxacin ototoxicity in guinea pigs

Antibiotic eardrops mostly contain potentially ototoxic aminoglycosides. Ciprofloxacin is an alternative, and there is limited experience in its topical use. To investigate the topical ototoxicity of ciprofloxacin, 11 guinea pigs have been operated on. Transbullae silicone drug delivery tubes were placed to both ears of the animals. After the operation the guinea pigs were divided into two groups. The first group of animals received 0.2 ml of 4% gentamicin in one ear and 0.2 ml of 0.9% sodium chloride solution in the other. The second group received 0.2 ml of 0.2% ciprofloxacin in the test ear and 0.2 ml of 0.9% sodium chloride solution in the control ear. All drugs were given once a day on 7 consecutive days. Auditory brainstem response thresholds were recorded using click, 4 and 8 kHz logon stimuli before and after the operation, and after topical drug application. Results were statistically compared using Wilcoxon matched pairs signed-ranks test. Comparison of the thresholds before and after the operation, physiological saline application, as well as ciprofloxacin application yielded no statistically significant differences, whereas application of gentamicin resulted in total hearing loss. The results indicate that topical use of 0.2% ciprofloxacin is not ototoxic in guinea pigs.     

Patterns of Brain Activity Associated With Variation in Voluntary Wheel-Running Behavior.

Rodents spontaneously run on wheels, but what underlies variation within and between species is unknown. This study used Fos immunoreactivity to compare brain activity in mice selectively bred for high wheel running (S) versus control (C) mice. Mice ran for 6 days, but on Day 7, half the mice were prevented from running. A strong positive correlation was found between running distance and Fos in the dentate gyrus of C runners that was lost in S runners. In mice prevented from running, Fos was higher in S than in C in the lateral hypothalamus, medial frontal cortex, and striatum. Results implicate specific brain regions in motivation to run and others in control of the intensity of the locomotor behavior itself. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased sensitivity to the locomotor depressant effect of a dopamine receptor antagonist during cocaine withdrawal in the rat

The effect of a dopamine receptor antagonist on locomotor activity was examined during withdrawal from either self-administered or experimenter-administered cocaine. In the self-administration experiment, the locomotor response to a challenge injection of cis-flupenthixol was assessed in photocell cages at 4 h after the cessation of a 12-h cocaine self-administration session. Rats which had self-administered cocaine, and were challenged with cis-flupenthixol (0.05 mg/kg), were found to be hypoactive relative to controls. In the experimenter-administered cocaine experiment, animals were given eight IP injections of 15 mg/kg cocaine over a 9.5-h period, for a total of 120 mg/kg. At 4, 8, and 24 h (tested in three separate groups of rats) after cessation of the eight injections, the locomotor response to a challenge injection of saline or cis-flupenthixol was tested. Cocaine-treated animals displayed a dose-dependent, heightened sensitivity to the locomotor depressant effects of 0.05 mg/kg and 0.2 mg/kg cis-flupenthixol 4 h post-cocaine, whereas they did not show increased sensitivity to 0.05 mg/kg cis-flupenthixol 8 or 24 h post-cocaine. However, cocaine-treated animals displayed a mild hypoactivity 8 h post-cocaine. In a separate group of animals, a dose-response experiment was performed which indicated that a dose of cis-flupenthixol as high as 0.2 mg/kg was required to produce locomotor depression in cocaine-naive rats. The results of this study support clinical observations of dopamine antagonist-precipitated motor dysfunction in abstinent cocaine abusers, and lend further support to the hypothesis that alterations in dopaminergic neurotransmission consequent to prolonged cocaine exposure are partly responsible for some of the symptoms of cocaine withdrawal.     

Cocaine sensitization can accelerate the onset of peak cocaine behavioral effects

The development of sensitization to the behavioral effects of cocaine occurs with repeated intermittent usage. In the present study rats were given five daily i.p. injections of cocaine (10 mg/kg) immediately prior to placement in an open-field environment for 20 min to induce cocaine sensitization. Control groups received saline injections or cocaine injections (10 mg/kg) 30 min after testing in the home cage. One week later the animals were given a challenge test with 10 mg/kg cocaine. The animals that had received cocaine in the test environment exhibited a more rapid onset of cocaine-induced behavioral effects than either animals previously treated with saline or animals that had received cocaine in the home cage. In a second experiment, the same sensitization protocol was followed except that during the interval between the end of the cocaine/saline treatments and the challenge test, the animals were given six daily 20-min saline tests to assess the contribution of differential habituation and/or Pavlovian conditioning to the sensitization effect. Neither habituation or Pavlovian conditioning altered the more rapid onset of cocaine stimulant effects induced by repeated cocaine treatments. It is suggested that the faster onset of cocaine effects is another way in which cocaine sensitization contributes to cocaine abuse liability.     

The role of voluntary exercise in enriched rearing: A behavioral analysis.

The effects of postweaning enriched rearing and home cage voluntary wheel-running exercise in adulthood were contrasted on a comprehensive battery of tests designed to assess mnemonic, attentional, emotional, and motor functions. In a 2 × 2 factorial design, female C57BL/6 mice were housed in groups in either standard or enriched cages, which were equipped with either a running or a locked wheel. They were maintained in the corresponding housing conditions for 2 months postweaning prior to, and throughout, testing. Enriched rearing was associated with anxiogenesis, hypolocomotor activity, enhanced motor skills, retarded extinction of conditioned responding, and improved water maze performance. Exercise as such enhanced motor coordination and facilitated extinction of contextual conditioning. Evidence for an interaction between enrichment and exercise was apparent in the open field test, conditioned freezing to a tone stimulus, prepulse inhibition, and acquisition of water maze reference memory. Hence, care should be taken to control for the unique contribution of wheel-running exercise when it is included as an integral component of the enrichment procedure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sound localization in chinchillas, III: Effect of pinna removal

Using a computerized infrared activity analysis system, the dose-response relationship, timing, and duration for stimulation of motor activity after a single dose of methylphenidate was studied in Sprague-Dawley rats. After 5 days of acclimation and 2 days of monitored baseline activity, rats received a single subcutaneous injection of vehicle or of 0.6, 2.5, 10 or 40 mg/kg methylphenidate 1 h into the dark cycle. Recording was then resumed for an additional 36 h. Five locomotor indices were analyzed. Each locomotor parameter monitored different aspects of motor activity. The doses of 2.5, 10 and 40 mg/kg significantly increased (P < 0.01) locomotor activity. The time to maximal effect (20, 50, and 90 min) and duration of effect (70, 210, and 280 min) increased with dose respectively. Ten mg/kg had the maximum effect on locomotor activity, while the largest dose, 40 mg/kg, elicited a more focused stereotyped activity that limited the amount of forward ambulation. Single injections of methylphenidate did not alter motor activity the next day. Pharmacological parameters and specific locomotor parameters describing the effects of methylphenidate at the beginning of the dark cycle can later be used in chronopharmacologic studies. They will also provide the basis for investigation of adaptive mechanisms during repeated or chronic administration of methylphenidate.     

Monoamine neurotoxins: selective and delayed effects on behavior in colonies of laboratory rats

Male laboratory rats were raised in two colonies, each of 27 rats, and then given intraventricular injections of the norepinephrine neurotoxin 6-hydroxydopamine (6-OHDA) or the serotonin neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) or saline. They were then returned to their enclosure and behavior during the next 50 days was observed. Shortly after neurotoxin injections the 6-OHDA rats spent more time in the burrows than controls and when out were inactive. The 5,6-DHT rats in contrast spent more time in the open than controls, ran more in activity wheels, approached humans, and fought more. Fighting, mounting, and hoarding in the colony gradually increased for 25 days; during this time the status of the 6-OHDA animals fell progressively whereas the 5,6-DHT animals increased in dominance. Social behavior returned to more normal levels after 50 days. Several successive stages of behavioral alterations occur following neurotoxin injections.     

A nonphotic stimulus inverts the diurnal-nocturnal phase preference in Octodon degus

Mechanisms differentiating diurnal from nocturnal species are thought to be innate components of the circadian timekeeping system and may be located downstream from the circadian pacemaker within the suprachiasmatic nucleus (SCN) of the hypothalamus. In the present study, we found that the dominant phase of behavioral activity and body temperature (Tb) is susceptible to modification by a specific modality of behavioral activity (wheel-running activity) in Octodon degus, a mammal that exhibits multiple chronotypes. Seven Octodon degus exhibited diurnal Tb and locomotor activity (LMA) circadian rhythms while entrained to a 24 h light/dark cycle (LD 12:12). When the diurnal animals were provided unrestricted access to a running wheel, the overt daily rhythms in these animals inverted to nocturnal. This nocturnal pattern was sustained in constant darkness and returned to diurnal after removal of the running wheel. Six additional animals exhibited nocturnal chronotypes in LD 12:12 regardless of access to running wheels. Wheel-running activity inverted the phase preference in the diurnal animals without changing the 24 hr mean LMA or Tb levels. Because wheel running did not increase the amplitude of the pre-existing diurnal pattern, simple masking effects on LMA and Tb cannot explain the rhythm inversion. The diurnal-nocturnal inversion occurred without reversing crepuscular-timed episodes of activity, suggesting that diurnal or nocturnal phase preference is controlled separately from the intrinsic timing mechanisms within the SCN and can be dependent on behavioral or environmental factors.     

Patterns of Brain Activation Associated With Contextual Conditioning to Methamphetamine in Mice.

Classical conditioning is thought to play a key role in addiction. The authors used c-Fos immunohistochemistry to demonstrate a conditioned physiological response to methamphetamine (meth) in mice. Male outbred mice were placed into an environment where they had previously experienced 2 mg/kg meth or saline. The meth-paired mice displayed increased c-Fos in several brain regions, including the nucleus accumbens, prefrontal cortex, orbitofrontal cortex, basolateral amygdala, and bed nucleus of the stria terminalis. No conditioned locomotor activity was observed, but individual activity levels strongly correlated with c-Fos in many regions. A batch effect among immunohistochemical assays was demonstrated. Results implicate specific brain regions in classical conditioning to meth and demonstrate the importance of considering locomotor activity and batch in a c-Fos study. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correlation of plasma corticosterone levels with running activity in the blinded rat

Blinded female reats were placed in running-wheel cages to monitor the phase of their activity cycle. After approximately a month of adaptation to the wheels, jugular vein blood samples were withdrawn at the beginning and end of the running phase of activity and analyzed for plasma corticosterone. By the time blood samples were obtained, the blined rats' activity cycles had desynchronized from the lighting cycle of the room in an apparently free-running fashion, and were out of phase with each other. The corticosterone levels were high at the beginning of the running phase and low at the end: begin run corticosterone was 34.5 +/- 13, end run corticosteronewas 14.2 +/- 10 (mean +/-SD in mug/100 ml of plasma; t = 7.93, df = 82, P less than 0.001). It was concluded that blinded rats do have an adrenocortical rhythm and that it is in phase with the activity cycle of each individual rat.     

Conditioned stimulus control in the rat circadian system depends on clock resetting during conditioning.

The authors examined the ability of a conditioned stimulus (CS; mild air disturbance) previously paired with an entraining light pulse to reset the circadian pacemaker in rats. Rats were entrained to a single 30-min light stimulus delivered every 25 hr or 24 hr (T cycle). Each daily light presentation was paired with the CS. After at least 20 days of stable entrainment to each of the T cycles, the rats were allowed to free run and were then presented with the CS at circadian time 15. CS-induced phase shifts in wheel-running activity rhythms were taken as evidence for conditioning. For the most part, conditioning occurred after CS-light pairings on the 25-hr but not 24-hr T cycle. The results suggest that CS control of the circadian clock phase depends on the effect that the entraining light pulse has on the clock during conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The interaction of thyroid state, MAOI drug treatment, and light on the level and circadian pattern of wheel-running in rats

In order to examine the relationship between thyroid status, the circadian system, and antidepressant drug response, the antidepressant drug clorgyline, a monoamine oxidase inhibitor (MAOI), was administered chronically to sham-operated or thyroparathyroidectomized rats. Wheel-running was monitored continuously in a light-dark (LD) cycle, and then in constant dim light. In LD, MAOI treatment increased levels of running. This effect was delayed in hypothyroid rats relative to euthyroid rats. In constant light, the MAOI-induced increase in running was diminished in euthyroid but not hypothyroid animals. Hypothyroid animals were less responsive to the change in lighting than were euthyroid animals, and this was more apparent in hypothyroid rats given MAOI. The daily pattern of running differed with lighting condition as well as with treatment group. MAOI-treatment of hypothyroid animals phase-advanced the pattern of wheel-running. MAOI-treatment of control animals increased the amplitude of wheel-running particularly in the LD cycle. These results indicate that thyroid status, lighting, and MAOI treatment interact to alter the behavioral response to chronic drug treatment.     

Laryngeal tuberculosis and laryngeal cancer

The primary objective of this study was to determine whether the development of behavioral sensitization to the putative dopamine D3 receptor agonist 7-OH-DPAT could be prevented by either selective D1-type or D2-type dopamine receptor antagonists. In three experiments, male Wistar rats (250-350 g) were given seven to nine injections (at 48-h intervals) of 7-OH-DPAT (1.0 mg/kg, SC) or vehicle in combination with the D2-type dopamine antagonist eticlopride (0.3 mg/kg, SC), the D1-type dopamine antagonist SCH 23390 (0.1 or 0.2 mg/kg, SC), or vehicle. After the injections, the rats were tested for locomotor activity in photocell arenas for 2 h. In the first two experiments, after seven injections, all rats were tested for activity following vehicle injections to test for possible conditioning effects. In each experiment, after the last pre-exposure session, all rats were given a challenge injection of 7-OH-DPAT (1.0 mg/kg, SC) and tested for activity. Major findings were as follows: a) 7-OH-DPAT treatments produced a progressively greater increase in locomotor activity with repeated treatment; b) concurrent treatment with eticlopride or SCH 23390 (0.1 and 0.2 mg/kg) blocked the acute locomotor-activating effects of 7-OH-DPAT across days; c) eticlopride, but not SCH 23390, completely blocked the development of behavioral sensitization to 7-OH-DPAT. Although the low dose of SCH 23390 (0.1 mg/kg) produced a partial attenuation of sensitization, the higher dose (0.2 mg/kg) of SCH 23390 appeared to augment, rather than block, sensitization to 7-OH-DPAT; d) rats previously treated with SCH 23390 (0.2 mg/kg, but not 0.1 mg/kg) without 7-OH-DPAT displayed a hyperactive response to the 7-OH-DPAT challenge injection; and e) after vehicle injections, rats previously given 7-OH-DPAT, SCH 23390, or eticlopride either alone or in combination were more active than vehicle control rats. These findings suggest that the neurochemical mechanisms mediating the development of behavioral sensitization to 7-OH-DPAT may differ from those of other dopamine D2-type agonists such as quinpirole or bromocriptine. Moreover, these results demonstrate that hyperactivity responses following vehicle injections in drug-pretreated animals do not necessarily reflect conditioning mechanisms.     

Exercise attenuates oral intake of amphetamine in rats

The effects of wheel running on oral intake of amphetamine were examined in six male Sprague-Dawley rats given a 0.075-mg/ml amphetamine sulfate solution as their sole source of liquid, six rats given a 0.15-mg/ml amphetamine solution, and four rats given water as their sole source of liquid. All animals were housed in Wahmann running wheels and adjoining cages, and had ad lib access to ground Purina Chow. For the first 7 days of the experiment, the doors to the running wheels were closed; the wheels were then opened for 6 days. This cycle was repeated a second time. Animals drinking the 0.15-mg/ml amphetamine solution consumed significantly less food and gained less weight than animals in the other two groups. Although there was no difference in food intake between rats drinking water and rats drinking the 0.075-mg/ml amphetamine solution, rats in the water group gained significantly more weight than rats in the 0.075-mg/ml amphetamine group. With respect to drug intake, rats consumed significantly less amphetamine when running in the wheels than when access to the wheels was prohibited. Access to running wheels did not alter water intake. These latter results suggest that drug intake can be reduced by the provision of an alternate behavior.     

Circadian rhythms of locomotor activity in the golden hamster (Mesocricetus auratus) measured with two different techniques.

Compared running wheels and spring-suspended cages as measurement devices for evaluating circadian locomotor activity rhythm. 12 golden hamsters were tested individually in a spring-suspended cage; 6 also had access to running wheels. Ss were exposed to 5 different levels of constant illumination, each condition lasting for several wks, and to a light-dark cycle. The onset of activity in the spring-suspended cage preceded the onset of activity in the running wheel by an amount which is a function of the circadian period. The increment by which the period changes in response to changes in light intensity equals, approximately, the changes of the interval between the 2 onsets. Animals with access to a running wheel show a tendency towards longer circadian periods. (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats

We have shown previously that footshock stress and priming injections of cocaine reinstate cocaine seeking in rats after prolonged drug-free periods (Erb et al., 1996). Here we examined the role of brain corticotropin-releasing factor (CRF) and the adrenal hormone corticosterone in stress- and cocaine-induced reinstatement of cocaine seeking in rats. The ability of footshock stress and priming injections of cocaine to induce relapse to cocaine seeking was studied after intracerebroventricular infusions of the CRF receptor antagonist D-Phe CRF12-41, after adrenalectomy, and after adrenalectomy with corticosterone replacement. Rats were allowed to self-administer cocaine (1.0 mg/kg/infusion, i.v) for 3 hr daily for 10-14 d and were then placed on an extinction schedule during which saline was substituted for cocaine. Tests for reinstatement were given after intermittent footshock (10 min; 0.5 mA) and after priming injections of saline and cocaine (20 mg/kg, i.p.). Footshock reinstated cocaine seeking in both intact animals and animals with corticosterone replacement but not in adrenalectomized animals. The CRF receptor antagonist D-Phe CRF12-41 blocked footshock-induced reinstatement at all doses tested in both intact animals and animals with corticosterone replacement. Reinstatement by priming injections of cocaine was only minimally attenuated by adrenalectomy and by pretreatment with D-Phe CRF12-41. These data suggest that brain CRF plays a critical role in stress-induced, but only a modulatory role in cocaine-induced, reinstatement of cocaine seeking. Furthermore, the data show that although reinstatement of cocaine seeking by footshock stress requires minimal, basal, levels of corticosterone, stress-induced increases in corticosterone do not play a role in this effect.     

Effects of intramuscular injections of selenium and vitamin E on selenium-vitamin E deficiency in young pigs

Effects of intramuscular injections of selenium and vitamin E on lesions in pigs with selenium-vitamin E deficiency syndrome were determined in 2 factorial experiments, using a total 69 pigs. The pigs were fed a selenium-vitamin E deficient, 22.3% protein ration, supplemented with methionine, minerals, and vitamins. Weekly intramuscular injections of isotonic saline solution, vitamin E, selenium, or vitamin E and selenium were given to the respective treatment groups. Selenium-vitamin E deficiency lesions occurred only in pigs that were given saline injections. Weekly intramuscular injections of either selenium (as selenous acid buffered to pH (7.3) at the rate of 0.05 mg/kg of body weight or vitamin E at the rate of 20 IU/kg of body weight or the combination of selenium and vitamin E prevented cardiac and skeletal myodegeneration, hepatic necrosis, and death. Significant increases of serum aspartate aminotransferase activity values were noted in pigs with liver, heart, or skeletal muscle lesions, but these increases were not correlated with the extent of the lesions. Vascular lesions, epicardial and endocardial hemorrhages, and yellow discoloration of body fat were not features of this experimentally induced disease. These lesions may be related to factors other than the deficiency of selenium, vitamin E, or selenium and vitamin E in rations previously used in reported studies.