Non-ambulatory Activity Research Articles

Blockade of Intranigral and Systemic D3 Receptors Stimulates Motor Activity in the Rat Promoting a Reciprocal Interaction among Glutamate, Dopamine, and GABA.

In vivo activation of dopamine D3 receptors (D3Rs) depresses motor activity. D3Rs are widely expressed in subthalamic, striatal, and dendritic dopaminergic inputs into the substantia nigra pars reticulata (SNr). In vitro studies showed that nigral D3Rs modulate their neurotransmitter release; thus, it could be that these changes in neurotransmitter levels modify the discharge of nigro-thalamic neurons and, therefore, motor behavior. To determine how the in vitro responses correspond to the in vivo responses, we examined the effect of intra-nigral and systemic blockade of D3Rs in the interstitial content of glutamate, dopamine, and GABA within the SNr using microdialysis coupled to motor activity determinations in freely moving rats. Intranigral unilateral blockade of D3R with GR 103,691 increased glutamate, dopamine, and GABA. Increments correlated with increased ambulatory distance, non-ambulatory activity, and induced contralateral turning. Concomitant blockade of D3R with D1R by perfusion of SCH 23390 reduced the increase of glutamate; prevented the increment of GABA, but not of dopamine; and abolished behavioral effects. Glutamate stimulates dopamine release by NMDA receptors, while blockade with kynurenic acid prevented the increase in dopamine and, in turn, of GABA and glutamate. Finally, systemic administration of D3R selective antagonist U 99194A increased glutamate, dopamine, and GABA in SNr and stimulated motor activity. Blockade of intra-nigral D1R with SCH 23390 prior to systemic U 99194A diminished increases in neurotransmitter levels and locomotor activity. These data highlight the pivotal role of presynaptic nigral D3 and D1R in the control of motor activity and help to explain part of the effects of the in vivo administration of D3R agents.

Monitoring non-ambulatory posture and activity using moment statistics and Bayesian classifier

Providing an appropriate care plan for the elderly to participate in everyday life activities is important, as is developing the technological means to support physical assessments. Current clinical protocol is generally periodic and subjective stemming from expert assessments and interviews. This paper aims to present a probabilistic framework to efficiently model the posture and activity of non-ambulatory elderly patients, provide evidence for quantitative measurements and assist in the health related quality of life (HRQL) assessment. Pressure distribution data gathered from a developed sensor pad were projected and parameterized using moment statistics as features for static and dynamic activity modeling. The effect of posture angle was reduced by estimation of linear regression and a rotation matrix is used to realign the orientation of posture. A Bayesian classifier with Gaussian mixture model was adopted for posture recognition. A robust decision method based on minimum classification error was applied for the parameter estimation. Several objective evaluations and field trials were performed to investigate the detection performance of posture and activity. Our proposed approach outperformed vector quantization and shows encouraging potential for the development of HRQL indicators.

Fluoxetine inhibits corticotropin-releasing factor (CRF)-induced behavioural responses in rats

Corticotropin-releasing factor (CRF) is a potent neuromodulator of stress-related behaviour but the neural mechanisms underlying these effects are not clear. Studies were designed to test the hypothesis that CRF-induced behavioural arousal involves interactions with brainstem serotonergic systems. To examine interactions between CRF and serotonergic systems in the regulation of behaviour, CRF (1 μg, intracerebroventricular (i.c.v.)) or vehicle was infused in the presence or absence of the selective serotonin re-uptake inhibitor fluoxetine (0, 0.1, 1 or 10 mg/kg, intravenous (i.v.)). Fluoxetine was used at these doses because it is known to decrease serotonin cell firing rates while increasing extracellular serotonin concentrations in select forebrain regions. We then measured behavioural, neurochemical and endocrine responses. CRF increased locomotion and spontaneous non-ambulatory motor activity (SNAMA) in the home cages. Fluoxetine decreased tissue 5-hydroxyindoleacetic acid concentrations, a measure of serotonin metabolism, in specific limbic brain regions of CRF-treated rats (nucleus accumbens shell region, entorhinal cortex, central nucleus of the amygdala). Furthermore, fluoxetine inhibited CRF-induced SNAMA. CRF and fluoxetine independently increased plasma corticosterone concentrations, but the responses had distinct temporal profiles. Overall, these data are consistent with the hypothesis that CRF-induced facilitation of behavioural activity is dependent on brainstem serotonergic systems. Therefore, fluoxetine may attenuate or alleviate some behavioural responses to stress by interfering with CRF-induced responses.

The transcription factors Nur77 and retinoid X receptors participate in amphetamine-induced locomotor activities

The major substrate underlying amphetamine (AMPH)-induced locomotor activity is associated with dopamine forebrain circuits. Brain regions associated with AMPH-induced locomotor activity express high levels of retinoid receptors. However, the role of these transcription factors in dopamine-mediated effects remains poorly understood. Two nuclear receptor families, the retinoic acid receptors (RAR) and the retinoid X receptors (RXR), transduce retinoic acid signal. RARs are specifically involved in retinoid signaling, whereas RXRs also participate in other signaling pathways as partners for other nuclear receptors such as Nur77, an orphan member of the nuclear receptor family expresses in dopamine system. To explore the role of retinoid receptors and Nur77 in AMPH-induced locomotor activity, we administered selective retinoid receptor drugs in combination with AMPH in adult wild-type and Nur77-deficient mice. At a low dose, AMPH similarly increased ambulatory activity in wild-type and Nur77-deficient mice, while it did not alter non-ambulatory activity. At a high dose, AMPH did not alter ambulatory activity anymore, while non-ambulatory activity strongly increased in wild-type mice. Nur77-deficient mice still displayed a higher ambulatory activity with no change in non-ambulatory activity. HX531, a synthetic RXR antagonist, blocks AMPH-induced ambulatory activity, whereas RAR drugs tested remained without effect. Interestingly, the effect of HX531 was abolished in Nur77-deficient mice, suggesting that this orphan nuclear receptor is essential for the action of the RXR drug. This study shows that RXR and Nur77 participate in AMPH-induced locomotor activity and prompts for further investigations on the role of Nur77 and RXR in addiction and reward-related behaviors.

Gonadal steroids mediate the opposite changes in cocaine-induced locomotion across adolescence in male and female rats

Evidence from both human studies and animal models indicates that cocaine elicits more behavioral stimulation in females than males. The present study sought to determine whether sex-specific responses to cocaine emerge during adolescence and to determine if gonadal steroid action during puberty affects adult responsiveness to cocaine. We administered cocaine using an escalating dose model in male and female rats at ages postnatal (PN) 28, 42, and 65 days. To assess the effects of pubertal gonadal steroid action, we compared the effects of binge cocaine administration on intact and prepubertally gonadectomized male and female rats in adulthood. Cocaine responses changed in opposite directions in males and females as they progressed through adolescence. At most doses, adolescent males were more responsive than adult males whereas adult females were more responsive than adolescent females. Ambulatory activity was age-dependent in males whereas non-ambulatory activity was age-dependent in females. Prepubertal gonadectomy increased behavioral responsiveness to the highest dose of cocaine in males whereas it decreased behavioral responsiveness to lower doses of cocaine in females. We conclude that sex differences in behavioral responses to cocaine arise during adolescence from a concurrent decrease in male responsiveness and increase in female responsiveness. Our results suggest that gonadal steroids exert lasting and opposing effects on the sensitivity of males and females to psychostimulants during development.

Motivated exploratory behaviour in the rat: The role of hippocampus and the histaminergic neurotransmission

Exploration is one of most basic adaptive behavioural responses, giving the animal an important evolutionary advantage to survive in a changing environment. Inspection of novel environments might be come with motivated exploratory behaviour. In spite that this type of exploration in the rat is known for many years, little attention has been given to the intrinsic mechanisms or the brain structures that are involved in. In the present work the hippocampus, the neurotransmitter histamine, and the geometrical features of novel objects were examined in a model of conflictive and non-conflictive exploration in the rat which evaluates incentive-motivated exploration. Young adult intact rats were tested in a neutral non-conflictive behavioural activity detector (OVM), with (eOVM) or without (sOVM) novel objects. Three different objects were used: a box, a toy duck, and a tower. Results show that animals decrease its general motor activity (horizontal, ambulatory and non-ambulatory activity) in favor to exploration of the objects. Motivated exploration was not the same for all three objects. Rats explored significantly more the Tower and the Box objects than the Duck item. Behavioral patterns of hippocampus-implanted rats showed decreased scores in motor activity but maintained the difference in the relation of “without/with objects” exploration. When hippocampus-implanted rats were tested in a conflictive exploration device (the elevated asymmetric plus-maze), exploration of the No Wall arm, considered the most fear-inducing environment, was significantly more explored by the animal when the tower object was positioned at its end than when it was absent. Microinjection into the ventral hippocampus of histamine abolished this motivated exploratory response. Pre-treatment with pyrilamine, and not with ranitidine, was effective to block the inhibitory effect of histamine on the object motivated exploration. Results confirm that the hippocampus is involved on incentive motivated exploration, and suggest that histamine is part of an analyzing neuronal circuit of novelty incentivating behavioural responses in rats.

But What About Swimming and Cycling? How to "Count" Non-Ambulatory Activity When Using Pedometers to Assess Physical Activity.

The aims of this study were to describe the amount of non-ambulatory physical activity (PA) undertaken by a sample of Australian workers, and to evaluate different methods of accounting for non-ambulatory activities when using pedometers to measure physical activity. Adults age 18 to 64 y (N = 204) wore a pedometer and recorded steps and non-step activity in a logbook for 7 d. Non-ambulatory activity was recorded by 28% of the participants (N = 52) with cycling and swimming the most frequently reported. The mean time reported for non-ambulatory activities was 82.8 (standard deviation 80.0) min/wk. On average, participants recorded 8873 (standard deviation 2757) steps/d. Time in non-ambulatory activities was converted to steps equivalents using three different conversion methods. Use of the three methods added 333 to 721 steps/d in the whole sample, but 1153 to 2566 steps/d for those who reported non-ambulatory activity. Suggestions are provided for accounting for non-ambulatory activities in interventions which rely on step count measures.

Neurotensin receptor activation sensitizes to the locomotor stimulant effect of cocaine: A role for NMDA receptors

This study was aimed at determining whether repeated activation of neurotensin receptors sensitizes to cocaine-induced locomotor activity and whether this effect can be prevented by blockade of N-methyl- d-aspartate receptors. Independent groups of male rats were injected on four occasions, every other day (training phase), with vehicle or one of two doses (4 and 8 mg/kg) of the NMDA antagonist CPP [(+/−)-3-(2-carboxypiperazine-4-yl)-propanephosphonic)] followed by an intracerebroventricular injection of 18 nmol/10 μl of d-Tyr[ 11]neurotensin, or its vehicle. Ambulatory, non-ambulatory and vertical movements were measured for 2 h on every test day. One week after the last day of the training phase, locomotor responses to a single injection of cocaine (7.5 mg/kg, ip) were measured in all rats; a second cocaine challenge test was performed 3 weeks post-training. Results show that during the training phase d-Tyr[ 11]neurotensin produced an initial suppression of all locomotor responses followed by an augmentation of ambulatory and non-ambulatory activity compared to controls, effects that were only slightly altered by CPP. Cocaine produced higher ambulatory and non-ambulatory activity in animals pre-exposed to neurotensin than in the vehicle pre-exposed animals, a sensitization effect that was not prevented by CPP at 1 week post-training but that was blocked at 3 weeks at the high dose. When given alone, the low dose of CPP produced an effect very similar to that of neurotensin on cocaine sensitization. These results further confirm that neurotensin plays a role in sensitization to psychostimulant drugs and suggests that NMDA receptors are involved in the long-term effect of exposure to neurotensin.

Modulatory role of catecholamines in the transsynaptic expression of c- fos in the rat medial prefrontal cortex induced by disinhibition of the mediodorsal thalamus: a study employing microdialysis and immunohistochemistry

We studied the interaction of catecholaminergic and thalamic afferents of the medial prefrontal cortex (PFC) by analyzing the effects of catecholamine depletion on thalamus-induced c- fos expression in the PFC of freely moving rats. Thalamic projections to the PFC were pharmacologically activated by perfusing the GABA-A receptor antagonist bicuculline (0.03 mM or 0.1 mM) through a dialysis probe implanted into the mediodorsal thalamic nucleus. Bicuculline perfusion induced Fos-like immunoreactivity in the thalamic projection areas, including the PFC, and in the thalamic nuclei surrounding the dialysis probe. 6-Hydroxydopamine lesions of the ventral tegmental area causing a 70–80% depletion of catecholamines in the PFC did not influence the increase in the number of Fos-like immunoreactive nuclei in the prefrontal cortex in response to thalamic stimulation. However, densitometric image analysis revealed that the intensity of Fos-like immunoreactivity in the PFC of lesioned rats perfused with 0.1 mM bicuculline was higher than in correspondingly treated controls. The behavioral activity to bicuculline perfusion, an increase of non-ambulatory activity (0.03 mM) followed by locomotion and rearing (0.1 mM), was not changed in 6-hydroxydopamine-lesioned rats. It is suggested that the thalamically induced c- fos response is directly mediated by excitatory, presumably glutamatergic, transmission and not indirectly by an activation of catecholaminergic afferents of the PFC. The increase in the intensity of Fos-like immunostaining in strongly stimulated, catecholamine-depleted rats suggests that catecholamines modulate the degree to which thalamic activity can activate the PFC of awake animals.

Behavioural actions of prolactin locally applied into the hippocampus of adult female rats.

The probable behavioural effects of rat prolactin (rPRL) locally applied into the ventral hippocampus (HPC) were studied in cycling female rats. Three experiments were performed examining the behavioural responses of rats subjected to three different situations: (i) Exploratory activity in an enriched holeboard (ii) exploratory activity under conflicting situation and (iii) escape behaviours in a forced swimming test. Behavioural parameters studied were: underground and object-directed exploration and locomotion (Experiment 1); latency time and exploration behaviours (Experiment 2); swimming time and escape behaviours (Experiment 3). In Experiment 1 results showed that rPRL decreased the underground exploration and also locomotion but increased the object-directed exploration and had no effect on non-ambulatory activity. In Experiment 2 results showed that treatment of rPRL increased the latency time but did not modify the exploratory activity. In Experiment 3 results showed that rPRL augmented the swimming time and one of two parameters (frequency of immersions intents) of the escape behaviour. Results are interpreted as local actions of PRL on hippocampal neuron affecting expression of behaviours of rats depending on the stressful conditions of the environment.

Nicotine withdrawal: a behavioral assessment using schedule controlled responding, locomotor activity, and sensorimotor reactivity.

Three different behavioral measures were used to assess the effects of abrupt cessation of chronic nicotine treatment. Nicotine (0, 3, or 6 mg/kg per day) was continuously administered for 12 days in rats by surgically implanting Alzet osmotic mini-pumps subcutaneously. Experiment 1 employed a light/dark discrimination task. There were no significant effects on number of responses or percent correct responding either during nicotine administration, or following cessation of nicotine. Experiment 2 examined ambulatory (locomotor) and nonambulatory activity. Chronic nicotine administration produced significant dose-dependent increases in both ambulatory and nonambulatory activity during the first 3 days of exposure. However, no significant alterations were seen in activity levels following nicotine cessation. Experiment 3 examined sensorimotor reactivity using the auditory startle response. During nicotine withdrawal, significant increases were seen in startle amplitude in both nicotine groups for 4 days. Nicotine (0.4 mg/kg, IP) administered before startle testing during the withdrawal phase attenuated the increased reactivity seen during nicotine cessation. These studies indicate that 1) rats display increased sensorimotor reactivity after cessation of chronic nicotine exposure, and 2) the expression of nicotine dependence and withdrawal is dependent on the behavioral task employed.