Preference For Compartment Research Articles

Fluoxetine rescues the depressive-like behaviour induced by reserpine and the altered emotional behaviour induced by nicotine withdrawal in zebrafish: Involvement of tyrosine hydroxylase.

Nicotine cessation leads to anxiety and depression. The suitability of the zebrafish model of anhedonia using reserpine and fluoxetine was evaluated. Fluoxetine was also used to reduce nicotine withdrawal-induced anhedonic state. Zebrafish were exposed to reserpine (40 mg/l) and then to fluoxetine (0.1 mg/l) for 1 week. Anhedonia was evaluated in the Novel Tank Diving and Compartment Preference tests. Another group was exposed to nicotine (1 mg/l/2 weeks) and then exposed to fluoxetine. Anxiety and anhedonia were evaluated 2-60 days after. Tyrosine hydroxylase (TH) immunoreactivity and microglial morphology (labelled by 4C4 monoclonal antibody) in the parvocellular pretectal nucleus (PPN), dorsal part, and of calcitonin gene-related peptide (CGRP) in the hypothalamus were also analysed. Less time in the top and increased latency to the top in reserpine compared to a drug-free group was found. Fluoxetine rescued reserpine-induced the reduced time in the top. Seven and 30 days after nicotine withdrawal more time in the bottom and similar time in the Compartment Preference test, rescued by fluoxetine, were shown. In the PPN, 30-day withdrawal induced an increase in TH immunoreactivity, but fluoxetine induced a further significant increase. No changes in PPN microglia morphology and hypothalamic CGRP were detected. Our findings validate the suitability of the zebrafish model of anhedonia using the reserpine-induced depression-like behaviour and the predictivity using fluoxetine. Fluoxetine rescued nicotine withdrawal-induced anhedonic state, opening the possibility to screen new drugs to alleviate anxiety and depression in smokers during abstinence.

Two Different Real-Time Place Preference Paradigms Using Optogenetics within the Ventral Tegmental Area of the Mouse.

Understanding how neuronal activation leads to specific behavioral output is fundamental for modern neuroscience. Combining optogenetics in rodents with behavioral testing in validated paradigms allows the measurement of behavioral consequences upon stimulation of distinct neurons in real-time with high spatial and temporal selectivity, and thus the establishment of causal relationships between neuronal activation and behavior. Here, we describe a step-by-step protocol for a real-time place preference (RT-PP) paradigm, a modified version of the classical conditioned place preference (CPP) test. The RT-PP is performed in a three-compartment apparatus and can be utilized to answer if optogenetic stimulation of a specific neuronal population is rewarding or aversive. We also describe an alternative version of the RT-PP protocol, the so-called neutral compartment preference (NCP) protocol, which can be used to confirm aversion. The two approaches are based on extensions of classical methodology originating from behavioral pharmacology and recent implementation of optogenetics within the neuroscience field. Apart from measuring place preference in real time, these setups can also give information regarding conditioned behavior. We provide easy-to-follow step-by-step protocols alongside examples of our own data and discuss important aspects to consider when applying these types of experiments.

Effects of Diazepam, Piracetam, and Mexidol on Passive Avoidance Response

Effects of the anxiolytic diazepam and nootropics piracetam and mexidol on passive avoidance conditioning (PAC) in rats were compared in experiments using a three-compartment apparatus. The latter consisted of a central, brightly lit compartment, a noxious dark compartment in which footshock was delivered to a rat, and a safe dark compartment, where the rat was not exposed to electric shock. Footshock during the acquisition of passive avoidance response in the control animals caused an abrupt increase in the latency to escape from the central compartment during testing but did not result in preference for a safe compartment. On the basis of these data on differential effects of footshock on PAC, we suggested that learning processes, which determined the motor response delay and the safe compartment preference, had a diverse associative nature. An increase in latency is associated with the classical fear conditioning regardless of the place of electric shock exposure. In contrast to this, the safe compartment preference is associated with the formation of the memory trace about the location of the footshock exposure. The use of pharmacological substances that affect fear and memory in different ways provided additional arguments in favor of the assumption about various associative processes determining passive avoidance learning. Reduction in the level of fear using diazepam decreased the latency of motor response compared to the control value but did not affect the preference for a safe compartment. In contrast, the mnemotropic properties of piracetam and mexidol increased the preference for a safe compartment without increasing the latency. These differential pharmacological effects confirm that PAC is based on the fear conditioning, which causes an increase in the latency to escape from the central compartment, and on the memory of the location of shock exposure, which provides the preference for the safe compartment.

Water column depth and light intensity modulate the zebrafish preference response in the black/white test

Currently, the black/white preference test has been used to evaluate anxiety-like behaviors in zebrafish. However, several inconsistent results have been reported across literature. Since animal behavior can be influenced by several environmental factors, the main goal of the present study was to investigate the influence of different water column depths and light intensities on zebrafish behavioral responses in the black/white test. On a 4cm water column depth, animals spent more time in the black than in the white compartment. However, when animals were tested in an 8cm water column, no significant difference was found. Using an inclined acrylic floor inside the aquarium, animals spent more time in the deep compartment when this was black. However, there is no difference in time spent in each compartment when the deeper compartment was white. For light intensity test, animals showed preference for the white compartment only when both compartments were illuminated with 100lx. For the others illumination settings, there was no difference in the compartment preference. In conclusion, our results suggest that variations in water column depth and light intensity can modulate zebrafish preference in the black/white test. These variations may be implicated in the discrepancies observed in literature.

Chronic NMDA receptor blockade in early postnatal period, but not in adulthood, impairs methamphetamine-induced conditioned place preference in rats

Early postnatal glutamatergic N-methyl-d-aspartate (NMDA) receptor blockade in animals is known to produce various behavioral deficits in adulthood. In the present study rats postnatally (day 7–20) treated chronically with MK-801, an NMDA receptor antagonist, were tested later in adulthood in methamphetamine (MAP)-induced conditioned place preference (CPP) using a unbiased procedure in a three-compartment apparatus. Rats with the same chronic treatment in adulthood were also tested. CPP test consisted of a baseline test before conditioning, place conditioning, and a preference test after conditioning. Rats postnatally treated with MK-801 did not show any evidence of preference for MAP-paired compartment compared with that for unpaired one in the preference test that was shown in rats postnatally treated with saline. On the other hand, rats treated with MK-801 in adulthood were not affected by the treatment and showed significant CPP as was shown in saline-treated control animals. Results suggest the possibility that chronic early postnatal, but not adulthood, NMDA receptor blockade induces persistent deficit of subsequent appetitive classical conditioning.

A high-fat diet impairs learning that is dependent on the dorsal hippocampus but spares other forms of learning.

Two experiments were conducted to evaluate the effects of a high-fat diet (HFD) on two tasks that were either dependent on the dorsal hippocampus (DH) or independent of the DH. A total of 80 adult male Sprague Dawley rats were administered either a lard-based HFD (60% of calories from fat) or a control diet (10% of calories from fat) for 8 weeks, and then were trained and tested on either the latent cue preference (LCP) task or the conditioned cue preference (CCP) task in a 3-compartment box apparatus (2 end-compartments and 1 middle-compartment). The end compartments of the box apparatus contained either a single environmental cue (DH-independent) or multiple environmental cues (DH-dependent). During training trials for the LCP and CCP tasks, on alternating days, rats were given access to water in 1 of the 2 end compartments and no water in the opposite end compartment. Rats were water-replete during LCP training and were water-deprived during CCP training. During testing for both tasks, all rats were water-deprived and given free access to all compartments while the amounts of time spent in each compartment were recorded. Results showed that rats given the HFD demonstrated no compartment preferences during both LCP and CCP testing when the compartments contained multiple cues, while rats fed the control diet demonstrated normal compartment preference behavior. However, when the compartments contained a single environmental cue, rats given either the HFD and control diet demonstrated normal LCP and CCP learning. These results demonstrate that consumption of a HFD disrupted both LCP and CCP learning in a multiple-cue (DH-dependent) environment, but did not impair either type of learning in a single-cue (DH-independent) environment. This may be due to selective impairment of the DH caused by increased oxidative stress, inflammation, and/or disrupted neurotransmission produced by consumption of the HFD.

Marginal Zone Macrophage Receptor MARCO Is Trapped in Conduits Formed by Follicular Dendritic Cells in the Spleen

The marginal zone (MZ) region of the spleen plays an important role in leukocyte traffic and the removal of blood-borne pathogens by resident macrophages. Macrophage receptor with a collagenous structure (MARCO), expressed by MZ macrophages, recognizes several microbial ligands and is also involved in the retention of MZ B cells. Here, we report that MARCO is also associated with follicular dendritic cells (FDCs) in the spleen. In its FDC-associated form MARCO is arranged in 0.3-0.5-μm diameter granular-fibrillar structures with an appearance similar to the white pulp conduit system formed by fibroblastic reticular cells (FRCs), but with different compartment preference. The follicular display of MARCO resists irradiation and requires the presence of both MZ macrophages and differentiated FDCs. The follicular delivery of MARCO is independent from the shuffling of marginal zone B cells, and it persists after clodronate liposome-mediated depletion of MZ macrophages. Our findings thus indicate that MARCO is distributed to both MZ and follicles within the spleen into conduit-like structures, where FDC-bound MARCO may mediate communication between the stromal microenvironments of MZ and follicles.

Concord grape juice reverses the age-related impairment in latent learning in rats

ObjectiveTwo experiments were conducted to determine if dietary supplementation with Concord grape juice could reverse the latent learning impairment normally observed in middle-aged male rats.MethodsBoth experiments utilized the latent cue preference (LCP) task, in which water-replete rats sample water in one compartment of a three-compartment box, and are subsequently given a compartment preference test when water-deprived to determine if they remember the compartment cue previously associated with water. In the first experiment, 40 male Sprague-Dawley rats (9, 10, 11, or 12 months old) were used to determine the age of onset of the impairment. In the second experiment, 24 male Sprague-Dawley rats (11 months old) were given daily access (10 ml/day) to 50% Concord grape juice, 50% white grape juice, or a calorically-equivalent sugar solution daily for 5 weeks prior to training.ResultsThe first experiment revealed that the latent learning impairment begins to manifest at 10 months of age in the male rats and is fully present at 11 months. The second experiment showed that rats that consumed the 50% Concord grape juice for 5 weeks beginning at 11 months of age showed intact latent learning in the LCP task, while rats that consumed the other two supplements showed the normal impairment on the LCP task.DiscussionThese results indicate that daily supplementation with Concord grape juice was able to reverse the latent learning impairment normally seen in middle-aged male rats. This reversal is most likely due to the presence of flavonoids in Concord grape juice.

A sex difference in the onset of the latent learning impairment in rats

The current study examined a sex difference in the onset of a latent learning impairment in Sprague-Dawley rats. Forty rats (20 male, 20 female) were tested on the Latent Cue Preference (LCP) task at 3 or 11 months of age. Additionally, 19 female rats were tested at 14 or 18 months of age. All rats were given four training trials in the LCP task using a three-compartment box, during which the rats explored a water-paired compartment and an unpaired compartment (each with a different visual cue) on consecutive days. Rats were then water-deprived for 23 hr and given a compartment preference test, in which more time spent in the water-paired compartment demonstrated latent learning. Results showed that 11-month old males and 18-month old females showed impaired latent learning, but 11- and 14-month old females showed intact latent learning, which may possibly be due to the neuroprotective effects of estrogen.

Modafinil alone and in combination with low dose amphetamine does not establish conditioned place preference in male sprague-dawley rats.

Modafinil is a novel wake-promoting drug with FDA approval for the treatment of narcolepsy, shift work sleep disorder, and sleep apnea. It is also prescribed for many off-label uses such as ADHD and it is currently being assessed as a treatment for psychostimulant dependence. Previous research assessing the abuse liability of modafinil in animals and humans suggests it is less potent and has a low abuse potential compared to traditional psychomotor stimulants. However, modafinil has not been carefully assessed in combination with other psychostimulant drugs. The current study used an unbiased place conditioning procedure simultaneously with locomotor screening procedures to assess the combined behavioral effects of modafinil and d-amphetamine in adult male Sprague-Dawley rats. Eight 30-min conditioning trials were conducted in a 2 compartment apparatus with distinct visual and tactile cues. Drug and vehicle conditioning trials were alternated with 1 trial per day separated by 24 hr. On drug conditioning trials, rats were administered either modafinil (64 mg/kg, i.g.), d-amphetamine (0.3 or 2.0 mg/kg, s.c.), a combination of modafinil (64 mg/kg) and d-amphetamine (0.3 mg/kg), or vehicle injections. On vehicle conditioning trials, all groups received vehicle injections. Preference for either compartment was assessed by recording time spent in each compartment during a 15-min test conducted 24 hr after the last conditioning trial. Results indicated that this low oral dose of modafinil did not significantly increase locomotor activity or establish conditioned place preference (CPP). Moreover, modafinil did not significantly alter the hyperlocomotor or CPP effects of d-amphetamine. To confirm that modafinil is behaviorally active at this low oral dose, a separate assessment of horizontal and vertical activity was conducted with male Sprague-Dawley rats in an open field apparatus. Results confirmed that modafinil increased locomotor activity relative to vehicle, with increases in vertical activity especially prominent, a measure that was not assessed in place conditioning trials. Although the current results predict a low abuse liability with concurrent use of modafinil and d-amphetamine, additional research with higher dose combinations may be warranted before ruling out the possibility that these drugs could have additive or synergistic effects.

Evaluating Preference-Seeking and Aversive Qualities of Salvia divinorum and Mitragyna speciosa

Use of botanicals for self-diagnosed conditions or recreational purposes is increasing. Many readily available botanicals are under-researched and little is known about potential liabilities. This study sought to utilize Conditioned Place Preference (CPP) to quantify rewarding or aversive properties of botanicals and their constituents in rats. This paradigm is based on the notion that animals prefer distinct environments previously paired with rewarding drugs [1]. Our approach to broadly characterize a botanical and its many constituents entails dose response functions of a plant extract, its fractions, and primary constituent(s). As a proof of concept, we chose two popular botanicals [2], one expected to produce place preference (Mitragyna speciosa) and the other expected to produce place aversion (Salvia divinorum). Because salvinorin A is well characterized as the major psychoactive compound, we did not study an extract fraction for S. divinorum. Following apparatus habituation and quantification of baseline compartment preference, male Sprague-Dawley rats were given eight drug-compartment conditioning trials which involved alternate day pairings of test compound to one compartment and vehicle to the other. This was followed by a compartment preference trial conducted under drug-free states. As expected, rats showed place preference to mitragynine similar to that of 1mg/kg (+)-Amphetamine. This effect was much less pronounced with the extract and its fractions. Rats showed robust place aversion to both Salvia divinorum and salvinorin A. These findings suggest that products that contain significant quantities of mitragynine pose a potential abuse liability.

Sensitivity to tactile novelty in the terrestrial isopod, Porcellio scaber

Invertebrates have been studied at biochemical, ecological, and behavioural levels, but current knowledge about the impact that learning may have on behaviour is rather sparse. The present study aimed to examine the sensitivity of isolated rough woodlice (Porcellio scaber, Latreille, 1804) to the tactile novelty of their environment. A simple way to test this issue was to refer to the place preference paradigm, traditionally used in vertebrates. In Experiment 1, woodlice were placed in a compartment for 30min in order to assess their ability to develop habituation in the absence of reward. In Experiment 2, woodlice were exposed to a compartment for 20min (habituation phase) and were then given free choice between that compartment and a novel compartment for 2min (preference phase). Depending on test conditions, rewards (humidity and/or shelter) were present or absent in the familiar compartment. The familiar and novel compartments differed with respect to the texture of the floor. In Experiment 3, the floor texture was the same in the two compartments in order to control for a novelty effect. The main results indicate that woodlice exhibited increased locomotion time, increased distance travelled, and increased speed in the novel compartment compared to the familiar compartment. There was no preference for either compartment when the floor textures of both were identical.

Preference for structured environment in zebrafish ( Danio rerio) and checker barbs ( Puntius oligolepis)

Information about the welfare and husbandry of pet and laboratory fish is scarce although millions of fish are sold in pet shops and used in laboratory research every year. Inadequate housing conditions can cause behavioural problems also in fish since they are complex animals with sophisticated behaviour. In this study, we investigated the influence of environmental complexity on compartment preference and behaviour in zebrafish ( Danio rerio) and checker barbs ( Puntius oligolepis). For the preference test, large aquaria were divided by two semi-transparent walls of Plexiglas into an empty compartment, a structured compartment enriched with plants and clay pots, and a smaller compartment in-between, where food was provided. For observation, the empty and structured compartments were divided into six zones of similar size by defining three vertical layers and two horizontal areas (back vs. front area). Seven groups of six to nine zebrafish and seven groups of seven or eight checker barbs were observed on four days each (within a time period of ten days) to assess compartment use and activity, and to assess behavioural diversity and use of zones within compartments. Both zebrafish and checker barbs showed a significant preference for the structured compartment. Nevertheless, in neither species did behavioural diversity differ between the empty and structured compartment. Zebrafish used all zones in both compartments to the same extent. Checker barbs, however, used the structured compartment more evenly than the empty compartment, where they mainly used the lower and middle zones. These results suggest that zebrafish and checker barbs have a preference for complex environments. Furthermore, they indicate that the behavioural and ecological needs of fish may vary depending on species, and recommendations for husbandry should be specified at species level.

The Activation of NMDA Receptor–ERK Pathway in the Central Amygdala is Required for the Expression of Morphine-Conditioned Place Preference in the Rat

Reinforcing effects of addictive drugs can be evaluated with the conditioned place preference (CPP) test which involves both the action of drugs and environmental cues. However, the encoded neural circuits and underlying signaling mechanism are not fully understood. In this study, we have used morphine-CPP model in the rat and characterized the role of N-methyl-D: -aspartate (NMDA) receptor and the phosphorylation of extracellular signal-regulated kinase (ERK) in the central nuclei of amygdala (CeA) in the expression of morphine-induced CPP. We have found that morphine repeated pairing treatment causes a significant preference for compartment paired with morphine after 1day or 7days post-training, which is associated with increased ERK1/2 phosphorylation (p-ERK1/2, a measure of ERK activity) in the CeA. More than 80% of the positive p-ERK1/2 neurons express NMDA receptor subunit NR1 by double immunofluorescence studies. The infusion of either MEK inhibitor U0126 or NMDA receptor antagonist MK-801 in the CeA not only suppresses the activation of ERK1/2 in the CeA but also abolishes the expression of CPP. These results suggest that the activation of the NMDA receptor-ERK signaling pathway in the CeA is required for the expression of morphine-induced place preference in the rat.

Deciphering the shape and deformation of secondary structures through local conformation analysis

BackgroundProtein deformation has been extensively analysed through global methods based on RMSD, torsion angles and Principal Components Analysis calculations. Here we use a local approach, able to distinguish among the different backbone conformations within loops, α-helices and β-strands, to address the question of secondary structures' shape variation within proteins and deformation at interface upon complexation.ResultsUsing a structural alphabet, we translated the 3 D structures of large sets of protein-protein complexes into sequences of structural letters. The shape of the secondary structures can be assessed by the structural letters that modeled them in the structural sequences. The distribution analysis of the structural letters in the three protein compartments (surface, core and interface) reveals that secondary structures tend to adopt preferential conformations that differ among the compartments. The local description of secondary structures highlights that curved conformations are preferred on the surface while straight ones are preferred in the core. Interfaces display a mixture of local conformations either preferred in core or surface. The analysis of the structural letters transition occurring between protein-bound and unbound conformations shows that the deformation of secondary structure is tightly linked to the compartment preference of the local conformations.ConclusionThe conformation of secondary structures can be further analysed and detailed thanks to a structural alphabet which allows a better description of protein surface, core and interface in terms of secondary structures' shape and deformation. Induced-fit modification tendencies described here should be valuable information to identify and characterize regions under strong structural constraints for functional reasons.

The entorhinal cortex, but not the dorsal hippocampus, is necessary for single‐cue latent learning

Two experiments were conducted to examine the roles of the entorhinal cortex (EC), dorsal hippocampus (DH), and ventral hippocampus (VH) in a modified Latent Cue Preference (LCP) task. The modified LCP task utilized one visual cue in each compartment, compared to several multimodal cues used in a previous version. In the single-cue LCP task, water-replete rats drink water in one compartment of the LCP box on 1 day, and then have no water in a second compartment of the LCP box the following day (one training trial), for a total of three training trials. Rats are then water-deprived prior to a preference test, in which they are allowed to move freely between the two compartments with the water removed. Latent learning is demonstrated when water-deprived rats spend more time in the compartment that previously contained the water. Experiment 1 demonstrated that the single-cue LCP task results in the same irrelevant-incentive latent learning as the multicue LCP task. In addition, Experiment 1 replicated the finding that a compartment preference based on this latent learning requires a deprivation state during the preference test, while a compartment preference based on conditioning does not. Experiment 2 examined the effects of pretraining neurotoxin lesions of the EC, DH, and VH on this single-cue LCP task. Results showed that lesions of the EC and VH disrupted the irrelevant-incentive latent learning, while lesions of the DH did not. These results indicate that a latent learning task that involves one discrete compartment cue, rather than several compartmental cues, does not require the DH. Therefore, the EC appears to play a central role in single-cue latent learning in the LCP task.

Adolescent male Wistar rats are more responsive than adult rats to the conditioned rewarding effects of intravenously administered nicotine in the place conditioning procedure

The initiation of smoking typically begins during adolescence, suggesting that nicotine may have different motivational effects during this developmental stage compared to adulthood. Studies using the conditioned place preference (CPP) procedure have demonstrated that adolescent rats are more sensitive to the conditioned rewarding effects of subcutaneously administered nicotine compared to adult rats, whereas intravenous self-administration studies have not demonstrated consistent age differences in the reinforcing effects of nicotine. This study was designed to evaluate if intravenously administered nicotine has age-dependent conditioned rewarding effects. Using an unbiased CPP procedure, adolescent and adult male Wistar rats were conditioned with one of two intravenous doses of nicotine that are sufficient to maintain self-administration (0.03 or 0.06mg/kg) or vehicle (saline) over a period of 8 conditioning trials (4 nicotine and 4 vehicle). Adolescent rats conditioned with 0.03mg/kg nicotine demonstrated a significant CPP, whereas adult rats did not at either dose tested. After 8 extinction trials, reinstatement of the CPP was observed following a nicotine priming injection (0.15mg/kg, s.c.) in adolescents that had previously been conditioned with 0.03mg/kg nicotine; vehicle-treated rats did not show a significant preference for either compartment. The present data are consistent with previous CPP studies using subcutaneously administered nicotine and suggest that passively administered intravenous nicotine is more rewarding in adolescent compared to adult rats.

Assessment of Symptomatic and Neuroprotective Efficacy of Mucuna Pruriens Seed Extract in Rodent Model of Parkinson’s Disease

Mucuna pruriens (MP) has long been used in Indian traditional medicine as support in the treatment of Parkinson's disease. However, no systematic preclinical studies that aimed at evaluating the efficacy of this substance are available to date. This study undertook an extensive evaluation of the antiparkinsonian effects of an extract of MP seeds known to contain, among other components, 12.5% L: -dihydroxyphenylalanine (L: -DOPA), as compared to equivalent doses of L: -DOPA. Moreover, the neuroprotective efficacy of MP and its potential rewarding effects were evaluated. The results obtained reveal how an acute administration of MP extract at a dose of 16 mg/kg (containing 2 mg/kg of L: -DOPA) consistently antagonized the deficit in latency of step initiation and adjusting step induced by a unilateral 6-hydroxydopamine lesion, whereas L: -DOPA was equally effective only at the doses of 6 mg/kg. At the same dosage, MP significantly improved the placement of the forelimb in vibrissae-evoked forelimb placing, suggesting a significant antagonistic activity on both motor and sensory-motor deficits. The effects of MP extract were moreover investigated by means of the turning behavior test and in the induction of abnormal involuntary movements (AIMs) after either acute or subchronic administration. MP extract acutely induced a significantly higher contralateral turning behavior than L: -DOPA (6 mg/kg) when administered at a dose of 48 mg/kg containing 6 mg/kg of L: -DOPA. On subchronic administration, both MP extract (48 mg/kg) and L: -DOPA (6 mg/kg) induced sensitization of contralateral turning behavior; however, L: -DOPA alone induced a concomitant sensitization in AIMs suggesting that the dyskinetic potential of MP is lower than that of L: -DOPA. MP (48 mg/kg) was also effective in antagonizing tremulous jaw movements induced by tacrine, a validated test reproducing parkinsonian tremor. Furthermore, MP induced no compartment preference in the place preference test, indicating the lack of components characterized by rewarding effects in the extract. Finally, in a subchronic mice model of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine hydrochloride (MPTP)-induced dopamine neuron degeneration, MP extract did not prove capable of preventing either tyrosine hydroxylase decrease induced by MPTP or astroglial or microglial activation as assessed by means of GFAP and CD11b immunohistochemistry, supporting the absence of neuroprotective effects by MP. Characterization MP extract strongly supports its antiparkinsonian activity.

A Reliable Behavioral Assay for the Assessment of Sustained Photophobia in Mice

Purpose: To develop a mouse behavioral assay that can assess differential nocioceptive sensitivity to light (photophobia). Materials and Methods: Normal C57BL/6J mice and congenic albino mice, C57BL/6J-Tyr c-2J/j, were habituated to a light/dark box testing chamber and then tested for a preference for the dark versus the light compartment in response to increasing brightness of the light compartment. Results: We found a statistically significant difference between the normal and the albino mice (N = 5/strain) in their preference for the dark compartment when the ambient condition in the light compartment was 1,000 lux, whereas at 0 lux, both groups of animals exhibited no preference for either compartment. Conclusions: The approach described here presents the first mouse behavioral assay for assessing aversion/avoidance behavior in response to light that appears to be comparable to human photophobia. This approach can be used to test other causes of sustained photophobia in mouse models, as well as to assess the efficacy of drugs for the relief of photophobia.

Methamphetamine-disrupted sensory processing mediates conditioned place preference performance

Drug memory plays an important role in priming subsequent drug use. We used drug-induced conditioned place preference (CPP) as a paradigm to study such drug memory. In this paradigm, repeated association of specific environmental cues with abused drug-induced subjective euphoria has been suggested to motivate later biased approaching behavior toward the euphoria-linked environment at a drug-free status. Our previous report indicated that formation of methamphetamine-induced CPP was independent of de novo protein synthesis. We suspected that methamphetamine-produced effects independent of its hedonic value may be responsible for the drug-induced place preference. One such possibility was that methamphetamine treatment directly disrupted the sensory encoding process and rodents’ novelty-seeking propensity consequently determined the biased place performance. We observed that mice undergoing three times of methamphetamine and compartment pairings exhibited similar compartment preference as those with only one or two methamphetamine-compartment pairings even though they all experienced three vehicle-compartment pairings. Moreover, 30 min before the CPP test, single methamphetamine injection at a dose of 1 mg/kg abolished methamphetamine (1 mg/kg)-induced CPP, while one dose of cocaine (5 mg/kg) did not affect cocaine (5 mg/kg)-induced CPP under a similar protocol. Finally, pretreatment with 1 mg/kg of methamphetamine impaired the spontaneous alteration and recognition performance in Y maze task and impeded the object recognition performance. Taken together, we conclude that methamphetamine-induced CPP performance may be, in part, caused by methamphetamine-impaired sensory processing.