Radiofrequency electromagnetic radiation exposure effects on amygdala morphology, place preference behavior and brain caspase-3 activity in rats.

The purpose of the study was to evaluate the changes in amygdala morphology and emotional behaviors, upon exposure to chronic RF-EMR in adolescent rats. Four weeks old male albino Wistar rats were exposed to 900 MHz (power density:146.60 µW/cm2) from a mobile phone in silent-mode for 28 days. Amygdala morphology was studied using cresyl violet, TUNEL and Golgi-Cox staining. Place preference behavior was studied using light/dark chamber test and following this brain caspase-3 activity was determined. Number of healthy neurons was decreased in the basolateral amygdala and cortical amygdala but not in the central amygdala after RF-EMR exposure. It also induced apoptosis in the amygdala. RF-EMR exposure altered dendritic arborization pattern in basolateral amygdala but not in the central amygdala. Altered place preference and hyperactivity-like behavior was evident after RF-EMR exposure, but brain caspase-3 activity did not change. RF-EMR exposure perturbed normal cellular architecture of amygdala and this was associated with altered place preference.

Lack of reliability in the disruption of cognitive performance following exposure to protons.

A series of three replications were run to determine the reliability with which exposure to protons produces a disruption of cognitive performance, using a novel object recognition task and operant responding on an ascending fixed-ratio task. For the first two replications, rats were exposed to head-only exposures to 1000 MeV/n protons at the NASA Space Radiation Laboratory. For the third replication, subjects were given head-only or whole-body exposures to both 1000 and 150 MeV/n protons. The results were characterized by a lack of consistency in the effects of exposure to protons on the performance of these cognitive tasks, both within and between replications. The factors that might influence the lack of consistency and the implications for exploratory class missions are discussed.

Interaction between age of irradiation and age of testing in the disruption of operant performance using a ground-based model for exposure to cosmic rays.

Previous research has shown a progressive deterioration in cognitive performance in rats exposed to (56)Fe particles as a function of age. The present experiment was designed to evaluate the effects of age of irradiation independently of the age of testing. Male Fischer-344 rats, 2, 7, 12, and 16 months of age, were exposed to 25-200 cGy of (56)Fe particles (1,000 MeV/n). Following irradiation, the rats were trained to make an operant response on an ascending fixed-ratio reinforcement schedule. When performance was evaluated as a function of both age of irradiation and testing, the results showed a significant effect of age on the dose needed to produce a performance decrement, such that older rats exposed to lower doses of (56)Fe particles showed a performance decrement compared to younger rats. When performance was evaluated as a function of age of irradiation with the age of testing held constant, the results indicated that age of irradiation was a significant factor influencing operant responding, such that older rats tested at similar ages and exposed to similar doses of (56)Fe particles showed similar performance decrements. The results are interpreted as indicating that the performance decrement is not a function of age per se, but instead is dependent upon an interaction between the age of irradiation, the age of testing, and exposure to HZE particles. The nature of these effects and how age of irradiation affects cognitive performance after an interval of 15 to 16 months remains to be established.

Lesions of the entopeduncular nucleus in rats prevent apomorphine-induced deficient sensorimotor gating.

Dopamine-induced hyperactivity and deficient sensorimotor gating, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR), are used as animal models for neuropsychiatric disorders such as schizophrenia and Tourette's syndrome. We here investigated whether excitotoxic lesions of the rat entopeduncular nucleus (EPN), the equivalent to the human globus pallidus internus (GPi), would improve apomorphine-induced PPI-deficits and hyperactivity. Additionally, we investigated the effect of EPN lesions on cognition, motivation and motor skills. In male Sprague Dawley rats bilateral EPN lesions were induced by stereotactic injection of ibotenate (4 µg in 0.4 µl phosphate buffered saline, PBS) or sham-lesions by injection of vehicle PBS. After one week, rats were tested for learning and memory (continuous and delayed alternation, T-maze), for motivation (progressive ratio test with breakpoint of 3 min inactivity, Skinner box), and for motor skills (rotating rod). Thereafter, rats were tested for PPI of ASR (startle response system) after subcutaneous injection of apomorphine (1.0mg/kg and vehicle) and for locomotor activity (0.5mg/kg and vehicle). Ibotenate-induced EPN lesions did not affect learning and memory, motivation or motor skills. Basal locomotor activity and PPI was also not affected, but EPN lesions ameliorated apomorphine-induced hyperlocomotion and deficient PPI. This work indicates an important role of the EPN for the modulation of dopamine agonist-induced deficient sensorimotor gating and hyperlocomotion, without affecting normal behavioral function.

Reducing hippocampal cell proliferation in the adult rat does not prevent the acquisition of cocaine-induced conditioned place preference.

Neurogenesis is important for developing certain forms of memory. Recently, hippocampal cell proliferation has been implicated in the development of drug addiction, an extreme form of emotional/motivational pathological memory. Aiming to explore the role of hippocampal neural cell proliferation in cocaine-induced conditioned place preference (CPP), we treated rats with whole brain X-irradiation, which substantially decreases the number of progenitor cells in the subventricular zone of the lateral ventricles and subgranular zone of the dentate gyrus. Surprisingly, there was no difference in the expression of cocaine-induced CPP. These results suggest that the existing neural network, rather than potential new neural circuits mediated by adult neurogenesis, is sufficient for the acquisition of cocaine-induced CPP.

A magnetic field effect on learning in male golden hamsters.

The aim of this experiment was to investigate the influence of repeated exposure to 10, 20, 30 or 40 Hz magnetic fields at 0.1T on the learning of male golden hamsters in a Skinner box, in which the animals learned to press a lever to receive a food reward. The latency of the first response was not affected by exposure to the magnetic fields used in this experiment. No significant field-dependent effects on the performance of the task were observed in males exposed to 10 and 20 Hz magnetic fields at 0.1T. However, exposure significantly improved the learning of the task in animals exposed to 30 and 40 Hz magnetic fields at 0.1T.

Changes in neuronal excitability serve as a mechanism of long-term memory for operant conditioning.

Learning can lead to changes in the intrinsic excitability of neurons. However, the extent to which these changes persist and the role they have in the expression of memory remain unclear. We found that in vitro analogs of operant conditioning produced a long-term (24 h) increase in the excitability of an identified neuron (B51) that is critical for the expression of feeding in Aplysia. This increase in excitability, which was cAMP dependent, contributed to the associative modification of the feeding circuitry, providing a mechanism for long-term memory.

Deep brain stimulation of the nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug seeking in rats.

Increasing evidence suggests that deep brain stimulation (DBS), which is currently being used as a therapy for neurological diseases, may be effective in the treatment of psychiatric disorders as well. Here, we examined the influence of DBS of the nucleus accumbens shell on cocaine priming-induced reinstatement of drug seeking, an animal model of relapse. Rats were allowed to self-administer cocaine (0.25 mg, i.v.) 2 h daily for 21 d and then cocaine-seeking behavior was extinguished by replacing cocaine with saline. During the reinstatement phase, DBS was administered bilaterally to the nucleus accumbens shell through bipolar stainless steel electrodes. Biphasic symmetrical pulses were delivered at a frequency of 160 Hz and a current intensity of 150 muA. DBS began immediately after a priming injection of cocaine (0, 5, 10, or 20 mg/kg, i.p.) and continued throughout each 2 h reinstatement session. Results indicated that only the higher doses of cocaine (10 and 20 mg/kg) produced robust and reliable reinstatement of cocaine seeking. DBS of the nucleus accumbens shell significantly attenuated the reinstatement of drug seeking precipitated by these higher cocaine doses. Additional experiments indicated that this DBS effect was both anatomically and reinforcer specific. Thus, DBS of the dorsal striatum had no influence on cocaine reinstatement and DBS of the accumbens shell did not affect the reinstatement of food seeking. Together, these results suggest that DBS of the nucleus accumbens shell may be a potential therapeutic option in the treatment of severe cocaine addiction.

Neurobiology of 50-kHz ultrasonic vocalizations in rats: electrode mapping, lesion, and pharmacology studies.

Fifty-kHz ultrasonic vocalizations have been proposed to reflect a positive appetitive affective state in rats, being consistently linked to the positive appetitive behavior. In the first study, we examined the brain substrates of 50-kHz ultrasonic vocalizations (USVs) by using localized electrical stimulation of the brain (ESB) at various sites that are known to mediate reward. We found that the brain areas that produced ESB-induced 50-kHz calls are the areas that have previously been shown to support the most vigorous self-stimulation behavior (prefrontal cortex, nucleus accumbens, ventral pallidum, lateral preoptic area, lateral hypothalamus, ventral tegmental area, and raphe). Importantly, all animals that showed repeatable ESB-induced 50-kHz USVs demonstrated self-stimulation behavior. In the second study, conditioned place preference was assessed following microinjection of the mu-opiate agonist Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol (DAMGO) directly into the ventral tegmental area (VTA) at a dose previously found to be rewarding. Animals that showed more 50-kHz USVs in response to drug injections compared to vehicle injections showed significant place preferences, whereas animals that did not show elevated vocalization to DAMGO did not show place preference. In experiment 3, we examined the effect of VTA electrolytic lesions, 6-OHDA lesions, and the effect of the D1/D2 dopamine antagonist flupenthixol (0 and 0.8 mg/kg, i.p.) on 50-kHz ultrasonic vocalizations. We found that these manipulations all selectively reduced 50-kHz ultrasonic vocalizations, and that these effects could be disassociated from any side effects. These data are consistent with the proposition that 50-kHz calls are tightly linked to reward in rats and that the neural circuit of 50-kHz calls closely overlaps that of ESB self-stimulation reward, drug reward, and the mesolimbic dopamine system.

Brief exposures to theta-burst magnetic fields impair the consolidation of food-induced conditioned place preference.

Theta-burst magnetic fields (1 microT) designed to mimic electrical stimuli employed in vitro to affect long-term potentiation have been previously shown to impair the acquisition of conditioned fear. In the current study, the authors were interested in investigating whether similar magnetic fields could affect the consolidation of food-induced conditioned place preference. Fourteen male Wistar rats were exposed to a theta-burst magnetic field (1 s pulse of 5 trains of an LTP-evoking pattern) continuously or with either a 5 s or 10 s interstimulus interval for 15 min immediately following 6 daily conditioning trials (15 min/day) in a place preference apparatus. Testing demonstrated the durations in the food-paired chamber was significantly shorter for all of the magnetic field-exposed groups compared to the sham-exposed group (they remained for longer periods in the food-paired chamber, typical of normal rats). In addition, the group exposed continuously to the LTP-magnetic field (1-ms interstimulus duration) displayed the least time in the food-paired chamber. The treatments explained 80% of the variance in durations within the experimental setting. These results suggest that exposures to theta-burst magnetic fields elicit amnesic effects for contextual stimuli.

Relative effectiveness of different particles and energies in disrupting behavioral performance.

On exploratory class missions to other planets, astronauts will be exposed to varieties and doses of heavy particles, which are not experienced in low earth orbit. These particles can affect neurobehavioral function and potentially interfere with the ability of astronauts to successfully meet mission requirements. While a significant amount of research has been performed on the relative biological effectiveness (RBE) of different types of heavy particles on cytogenetic function, little research has been done on the effectiveness of different particles on central nervous system function and on cognitive/behavioral performance. The present paper reviews some recent research on the effects of exposure to different types and energies of heavy particles on the performance of two behavioral tasks which depend upon the integrity of the central dopaminergic system. This review indicates that the RBE of different particles for neurobehavioral dysfunction cannot be predicted only on the basis of the linear energy transfer of the specific particle.

Regional characteristics of electrical responses (in the band 1-225 Hz) in the cerebral cortex to conditioned stimuli in operant conditioning.

Power spectra of short-term (less than 1 sec) electrical responses to conditioned stimuli were studied over the frequency range 1-225 Hz in dogs during food-related operant conditioning. These spectra demonstrated regional characteristics in terms of energy levels and frequency composition. Responses were more marked in the visual and parietal areas of the left hemisphere. Power in responses to a differential stimulus were significantly lower than with responses to positive stimuli, mainly because of the high-frequency range (80-225 Hz); energy levels in these two situations were similar during prestimulus intervals. The frequency composition of responses was defined by a series of discrete frequencies in the gamma (30-80 Hz) and high-frequency ranges.

A longitudinal study of operant responding in rats irradiated when 2 months old.

Two-month-old rats were exposed to 56Fe particles (1, 1.5, 2 Gy; 1 GeV/nucleon). They were tested on the performance of an ascending fixed-ratio operant task (bar pressing for food reward) at 7, 11 and 15 months after irradiation. Previous research had shown that for the same rats tested at 3 months after exposure, only the rats exposed to 2 Gy of 56Fe particles showed a significant disruption of performance compared to control (0 Gy) rats. When these rats were tested 7, 11 and 15 months after exposure, all irradiated groups showed significantly poorer performance than the controls. These results suggest that there is an interaction between irradiation and age such that 56Fe-particle-induced performance deficits can develop several months after exposure.

Effects of age and diet on the heavy particle-induced disruption of operant responding produced by a ground-based model for exposure to cosmic rays.

On missions to other planets, astronauts will be exposed to galactic cosmic rays which are composed of heavy particles (such as 56Fe) and protons. Exposure to these particles can affect the ability of rats to perform a variety of tasks, indicating that there is the possibility that the performance capabilities of astronauts may be affected. Previous research has shown that diets containing blueberry or strawberry extract can ameliorate the deficits produced by irradiation using a ground-based analog for exposure to cosmic rays. Rats were placed on diets containing 2% blueberry or strawberry extract for 2 months prior to exposure to 1.5 Gy of 1 GeV/n 56Fe particles. There were no effects on performance of any group of animals when tested on an ascending fixed-ratio operant task 6 months following exposure. When tested 12 months after exposure, the performance of the radiated animals given blueberry extract did not differ from the radiated animals fed the control diet. Both groups performed significantly poorer than the non-irradiated controls. There were no differences between the non-irradiated animals fed control diet and the radiated animals fed the strawberry diet and their performance was significantly better than of the radiated rats fed the blueberry or control diets. The results indicate that diets containing strawberry extract may provide a significant level of radiation protection on exploratory class missions.

Repeated peripheral electrical stimulations suppress both morphine-induced CPP and reinstatement of extinguished CPP in rats: accelerated expression of PPE and PPD mRNA in NAc implicated.

Previous studies have shown that peripheral electrical stimulation (PES) can suppress morphine-induced conditioned place preference (CPP) and the reinstatement of extinguished CPP in the rat. The present study was performed to elucidate if preproenkephalin (PPE) and preprodynorphin (PPD) mRNAs in the nucleus accumbens (NAc) play a role in this event. Rats were trained with morphine for 4 days to establish CPP paradigm. They were then given 15-min test once a day for eight consecutive days for extinction trial. Twenty-four hours after the 8th session of extinction trials, rats were given peripheral electrical stimulation (PES) at 2 or 100 Hz once a day for 3 days, then a morphine-priming injection at a dose of 1, 2, or 4 mg/kg to reinstate the extinguished CPP. At the end of the experiment, PPE and PPD mRNA levels in the nucleus acccumbens (NAc) were determined by the semiquantitative RT-PCR technique. The results showed that PES at 2- and 100-Hz administered 30 min a day for 3 days suppressed both the expression of morphine-induced CPP and the reinstatement of extinguished CPP. PES at 2 Hz increased preproenkephalin (PPE) mRNA levels, whereas PES of 100 Hz that of preprodynorphin (PPD) mRNA levels in the NAc. These findings suggest that enkephalin and dynorphin in NAc may play important roles in the mechanisms underlying the inhibitory effect of PES on the expression and reinstatement of morphine-induced CPP in rats.

Acetylcholine release in the hippocampus during the operant conditioned reflex and the footshock stimulus in rats.

The activity of the septo-hippocampal cholinergic pathway was investigated by measuring changes in the extracellular acetylcholine (ACh) levels in the hippocampus, by means of microdialysis, during the operant conditioned reflex and the repeated footshock stimulus. Microdialysis samplings were conducted in a Skinner box where lights were delivered as conditioned stimuli (CS) paired with footshocks as unconditioned stimuli (US). Two groups of rats were used. Extracellular ACh and choline (Ch) in samples collected at 6min intervals were assessed by high-performance liquid chromatography with electrochemical detection. The elevation of hippocampus ACh was observed in the two experimental groups. The increase in ACh during aversive stimulus (footshock) was significantly larger and was probably related to the number of footshocks. There might be moderate increase in the hippocampal ACh release during the retrieval of information. The concentration of choline showed no significant fluctuation in the two groups during the whole process. This experiment explored in more detail hippocampal cholinergic activity in relation to the two different procedures.

[Comparative estimation of the effects of continuous and intermittent cyclical microwave radiation on the behavior of rats in the extraordinary situation]. / Sravnitel'naia otsenka vliianiia mikrovolnogo izlucheniia teplovoi intensivnosti v nepreryvnom i tsiklicheskom rezhimakh na povedenie krys v ékstremal'noi situatsii.

Research has been carried out to investigate the effects of pulsed microwave exposure without pause (7 GHz, 400 pps, 100 microseconds, 70-150 mW/cm2, exposure 10 min) and pulsed interrupted cyclical microwave exposure (5 min exposure--4 min pause--5 min exposure) on learned behaviors of rats in the paradigm of extraordinary situation (the rescue of the life). It was shown that reductions in conditioned behavior after acute pulsed microwave exposure occurred at SAR of 21 W/kg (100 mW/cm2) and after cyclical pulsed microwave exposure at SAR of 28.4 W/kg (135 mW/cm2).

[Effects of microwave radiation on conditioned behavior of rats]. / Vliianie mikrovolnogo oblucheniia na uslovnoreflektornuiu deiatel'nost' krys.

Research has been carried out to investigate the effects of microwave exposure (7 GHz, surface energy density 10-50 mW/cm2, SAR 2.1-10.5 W/kg) on learned behaviors of rats in the paradigm of conditioned avoidance reflex. It was shown that transitory reductions in conditioned behavior after acute microwave exposure occurred at an SAR equal to the intensity of rat basal metabolism. It was found cumulative effects for intermittent exposures of rats at a power density of 10 mW/cm2.

Effects of exposure to 56Fe particles or protons on fixed-ratio operant responding in rats.

On long-duration trips outside of the magnetosphere, astronauts will be exposed to protons and to heavy particles which can affect their performance of required tasks. It is essential to determine the range of behaviors that might be affected by exposure to these types of radiation in order to understand the nature of behavioral deficits and to develop effective countermeasures. The present experiment examined the ability of rats to make an operant response following exposure to protons (250 MeV, 4 Gy) or 56Fe particles (1 GeV/n, 1 or 2 Gy). Following irradiation, rats were trained to press a lever in order to obtain food reinforcement. They were then placed on an ascending fixed-ratio schedule from FR-1 (each lever press rewarded with a food pellet) through FR-35 (35 lever presses required for 1 food pellet). Rats exposed to 4 Gy of protons or 1 Gy of 56Fe particles responded similarly to controls, increasing their rate of responding as the ratio increased. However, rats exposed to 2 Gy of 56Fe particles failed to increase their rate of responding at ratios greater than FR-20, indicating that rats exposed to 2 Gy of 56Fe particles cannot respond appropriately to increasing work requirements.