Voice disorders manifest in the early stages of Parkinson disease (PD), suggesting the vulnerability of the laryngeal sensorimotor system to mild alterations in dopamine signaling. Previous research has demonstrated that manipulations of central dopamine result in acoustic changes in rat ultrasonic vocalization (USV) and selective manipulation of receptor subtypes results in dose dependent changes in call rate and complexity. However, no study has specifically focused on the influence of dopamine receptor subtypes on acoustic features of USV production. This study examined the influence of D1 and D2 receptor subtypes on voluntary laryngeal sensorimotor control (USV) and gross whole-body involvement. Rat USV acoustics and catalepsy descent time were analyzed following the administration of selective D1 and D2 receptor antagonists in isolation and in combination, and a vehicle control. Results support the hypothesis that degradations of the acoustic signal would be most severe following combined receptor antagonism (D1+D2) compared with D1 or D2 receptor antagonism alone, and the vehicle (saline) condition. In addition, results indicate that selective D1 receptor antagonism alters acoustic parameters to a greater extent than D2 receptor antagonism. Thus, dopamine receptor subtypes appear to influence acoustic parameters to different degrees. Catalepsy descent time was longest following combined dopamine receptor antagonism but was also significantly increased with selective D1 or D2 antagonism. Together, these results support the potentially different contributions receptor subtypes play in cranial and limb sensorimotor control.

Fluoxetine (FLX) is commonly used to treat anxiety and depressive disorders in pregnant women. Since FLX crosses the placenta and is excreted in milk, maternal treatment with this antidepressant may expose the fetus and neonate to increased levels of serotonin (5-HT). Long-term behavioral abnormalities have been reported in rodents exposed to higher levels of 5-HT during neurodevelopment. In this study we evaluated if maternal exposure to FLX during pregnancy and lactation would result in behavioral and/or stress response disruption in adolescent and adult rats. Our results indicate that exposure to FLX influenced restraint stress-induced Fos expression in the amygdala in a gender and age-specific manner. In male animals, a decreased expression was observed in the basolateral amygdala at adolescence and adulthood; whereas at adulthood, a decrease was also observed in the medial amygdala. A lack of FLX exposure effect was observed in females and also in the paraventricular nucleus of both genders. Regarding the behavioral evaluation, FLX exposure did not induce anhedonia in the sucrose preference test but decreased the latency to feed of both male and female adolescent rats evaluated in the novelty-suppressed feeding test. In conclusion, FLX exposure during pregnancy and lactation decreases acute amygdalar stress response to a psychological stressor in males (adolescents and adults) as well as influences the behavior of adolescents (males and females) in a model that evaluates anxiety and/or depressive-like behavior. Even though FLX seems to be a developmental neurotoxicant, the translation of these findings to human safe assessment remains to be determined since it is recognized that not treating a pregnant or lactating woman may also impact negatively the development of the descendants.

The ability to update and modify previously learned behavioural responses in a changing environment is essential for successful utilization of promising opportunities and for coping with adverse events. Valid models of cognitive flexibility that contribute to behavioral flexibility include set-shifting and reversal learning. One immediate effect of acute stress is the selective impairment of performance on higher-order cognitive control tasks mediated by the medial prefrontal cortex (mPFC) but not the hippocampus. Previous studies show that the mPFC is required for set-shifting but not for reversal learning, therefore the aim of the present experiment is to assess whether exposure to acute stress (15min of mild tail-pinch stress) given immediately before testing on either a set-shifting or reversal learning tasks would impair performance selectively on the set-shifting task. An automated operant chamber-based task, confirmed that exposure to acute stress significantly disrupts set-shifting but has no effect on reversal learning. Rats exposed to an acute stressor require significantly more trials to reach criterion and make significantly more perseverative errors. Thus, these data reveal that an immediate effect of acute stress is to impair mPFC-dependent cognition selectively by disrupting the ability to inhibit the use of a previously relevant cognitive strategy.

Alcohol consumption during pregnancy has deleterious effects on the developing foetus ranging from subtle physical deficits to severe behavioural abnormalities and are encompassed under a broad umbrella term, Foetal Alcohol Spectrum Disorders (FASD). High levels of exposure show distinct effects, whereas the consequences of moderate exposures have been less well studied. The aim of this study was to examine the effects of a moderate dose ethanol exposure using an ad libitum drinking procedure during the first eight days of gestation in mice on the behavioural phenotype of adult offspring. Adult female C57Bl/6J mice were mated and exposed to either 10% (v/v) ethanol or water for the first 8 days of gestation (GD0-8), and then offered water for the rest of gestation. Early developmental milestone achievement was assessed in offspring at postnatal days (P) 7, 14 and 21. Adult offspring underwent a comprehensive battery of behavioural tests to examine a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception, as well as spatial memory in a water maze. Ethanol-exposed mice had similar postnatal developmental trajectories to water-exposed mice. However, the ethanol-exposed mice showed increased hyperlocomotion at P 14, 21 and 70 (p<0.05). Increased exploration and heightened motivation were also observed in adult mice. Furthermore, ethanol-exposed mice showed a significant improvement in memory in the water maze. The main findings were that mice had persistent and long lasting alterations in behaviour, including hyperactivity and enhanced spatial memory. These data suggest that even moderate dose ethanol exposure in early gestation has long term consequences on brain function and behaviour in mice.

The zebrafish has been proposed for the study of the effects of ethanol on the vertebrate brain. Behavioural tests have been successfully employed in the phenotypical characterization of these effects. However, the short scale (minute to minute) time course of ethanol induced changes of zebrafish behaviour has not been analyzed. The current study alleviates this need using a 2×3 chronic x acute ethanol exposure experimental design. We first expose zebrafish to ethanol chronically using a dose escalation procedure in which fish are kept in a final concentration of 0.5% vol/vol ethanol for 10 days while control fish receive identical dosing procedures but no ethanol. Subsequently, we expose zebrafish for one hour to an acute dose of ethanol (0.00, 0.50, or 1.00% vol.vol) and monitor their behaviour throughout this. period. We quantify the mean and within-individual temporal variance of distance travelled, distance from bottom and angular velocity using video-tracking, and establish temporal trajectories of ethanol induced behavioural changes in zebrafish. For example, we find fish of the highest acute dose group previously not exposed to chronic ethanol to exhibit an inverted U shaped temporal trajectory in distance travelled (biphasic alcohol effect). We find this response to be blunted after chronic ethanol exposure (development of tolerance). We also describe an acute ethanol withdrawal induced increase in angular velocity. We conclude that temporal analysis of zebrafish behaviour is a sensitive method for the study of chronic and acute ethanol exposure induced functional changes in the vertebrate brain.

Although a series of amino acid analogues have been shown to modulate brain function, information on the pharmacology of alpha-alkylated amino acids (AAAA) is limited. In particular there is no information on the effect of these amino acid analogues (AAA) on the elevated plus maze, the tail suspension test and the forced swim test. It was therefore the aim of the study to test a series of AAAA in these paradigms in order to explore behavioral activities of this compound class. 10 male mice per group aged between 10-14 weeks were used. Vehicle-treated controls were used in addition to intraperitoneal injections of 1, 10 and 100mg/kg body weight of each, alpha-amino-isobutyic acid (AIB), isovaline (IVA), alpha-propyl-alanine (APA), alpha-butyl-alanine (ABA), alpha-pentyl-alanine (APnA), alpha-ethylphenylglycine (AEPG) and alpha-methyl-valine (AMV). The elevated plus maze (EPM), the tail suspension test (TST) and forced swim test (FST) were used for behavioral testing. There were dose-dependent results: all compounds increased time and pathlength in the open arm of the EPM at least at one dose administered. In the TST and in the FST only the 100mg dose was showing an effect. The results show pharmacological activity modifying the EPM in low doses suggesting the use in treatment of behavioral traits and symptoms represented by or linked to the EPM including anxiety-related behaviour including depression. Compounds acting at higher doses may be used to induce behavioral changes and thus serve as neurobiological-neuropharmacological tools.

Behavioral experience, in the form of skilled limb use, has been found to impact the structure and function of the central nervous system, affecting post-stroke behavioral outcome in both adaptive and maladaptive ways. Learning to rely on the less-affected, or non-paretic, body side is common following stroke in both humans and rodent models. In rats, it has been observed that skilled learning with the non-paretic forelimb following ischemic insult leads to impaired or delayed functional recovery of the paretic limb. Here we used a mouse model of focal motor cortical ischemic injury to examine the effects of non-paretic limb training following unilateral stroke. In addition, we exposed some mice to increased bimanual experience in the home cage following stroke to investigate the impact of coordinated dexterous limb use on the non-paretic limb training effect. Our results confirmed that skilled learning with the non-paretic limb impaired functional recovery following stroke in C56BL/6 mice, as it does in rats. Further, this effect was avoided when the skill learning of the non-paretic limb was coupled with increased dexterous use of both forelimbs in the home cage. These findings further establish the mouse as an appropriate model in which to study the neural mechanisms of recovery following stroke and extend previous findings to suggest that the dexterous coordinated use of the paretic and non-paretic limb can promote functional outcome following injury.

Drug use typically begins during adolescence, which is a period of ongoing neurobiological development that may confer heightened vulnerability to develop drug dependence. Previously, our lab has shown that amphetamine (AMPH)-induced deficits in a medial prefrontal cortex (mPFC)-sensitive working memory task are greater in rats exposed to the drug during adolescence compared to adulthood. Here, we examine potential age-dependent effects of AMPH exposure on behavioral flexibility tasks that are sensitive to disruptions in mPFC and orbitofrontal cortex (OFC) function. Male Sprague-Dawley rats were injected (i.p.) with saline or 3mg/kg AMPH every other day between postnatal days (PNDs) 27-45 and PNDs 85-103. Starting around PND 125, rats were tested in an attentional set-shifting task and a subset of those was then tested in an operant strategy shifting task. Following completion of the operant task, rats were challenged with 3mg/kg AMPH and monitored in open field chambers. Our results demonstrate that AMPH-exposed rats were faster to acquire simple and compound discriminations, but were impaired during the first stimulus-reward reversal when compared to controls. In the operant strategy shifting task, adolescent-exposed rats shifted more rapidly between strategies and completed reversals faster than adult-exposed and control rats, respectively. The final AMPH challenge revealed evidence for sensitization in drug pre-exposed rats, with adult-exposed animals exhibiting the most significant effects. Together, these results suggest that AMPH induces long-lasting changes in behavioral flexibility that are at least partially dependent on age of exposure and may be due to adaptations in OFC function.

Aging is usually associated with a progressive disruption of the redox balance leading to recurrent damage resulting from oxidative stress. Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of motor behavior disorders. Therefore, antioxidant therapies have received considerable attention in motor behavior defects treatment. The nuclear factor erythroid 2-related factor 2 (Nrf2) binds to antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes under conditions of oxidative stress, which reduces oxidative stress and accumulation of toxic metabolites. Testosterone has many physiological and behavioral effects throughout the lifespan and shown to affect motor behavior in adult male rats and gonadectomized rats. However, whether Nrf2-ARE pathway is activated after testosterone administration has not been studied in aged rats. The tilting-plane test and the horizontal-wire test as well as the oxidative stress parameters, the expression of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) and the number of tyrosine hydroxylase immunoreactive (TH-ir) cells in brain were examined in aged rats following chronic subcutaneous injections of testosterone propionate (TP). Our study shown that chronic TP supplement significantly ameliorated the decline of balancing reactions and muscular strength associated with aging. Oxidative stress parameters were ameliorate, the expression of Nrf2, HO-1 and NQO1 at protein or gene levels and the number of TH-ir cells significantly increased in substantia nigra or caudate putamen after TP treatment in aged rats. Our findings demonstrated that chronic TP treatment activated Nrf2-ARE pathway may influence the maintenance of the balancing reactions and muscular strength and reduce TH-ir cells death in aged rats. Therefore, TP supplement have shown for therapeutic strategies in the treatment and modification of motor behavior disorders.

We report a functional magnetic resonance imaging (fMRI) study of healthy adult participants who completed a demanding Go/NoGo task. The primary purpose of this study was to delineate the neural systems underlying successful and unsuccessful response inhibition using a large sample (N=102). We identified a number of regions uniquely engaged during successful response inhibition, including a fronto-parietal network involving the anterior cingulate, supplementary motor areas, lateral and inferior prefrontal regions, and the inferior parietal lobule. Unique hemodynamic activity was also noted in the amygdala and in frontostriatal regions including the inferior frontal gyrus and portions of the basal ganglia. Also, contrasts were defined to explore three variants of hemodynamic response allowing for more specificity in identifying the underlying cognitive mechanisms of response inhibition. Addressing issues raised by prior small sample studies, we identified a stable set of regions involved in successful response inhibition. The present results help to incrementally refine the specificity of the neural correlates of response inhibition.