Nabiximols (NBX) suppresses tremor in a rat Harmaline model of essential tremor.

Background: Essential tremor (ET) is one of the most prevalent movement disorders; despite this, there remains an unmet need for novel therapies. The treatment of rats with harmaline modulates the rhythmicity of inferior olivary neurons, resulting in generalized tremor with a frequency of 9-12 Hz in rats, comparable to that of human ET (4-12 Hz).

Purpose: Interestingly, cannabinoids reduce tremor, therefore we have assessed the cannabinoid nabiximols (NBX; marketed as Sativex) a complex botanical drug mixture, in the harmaline-rat model of ET.

Food restriction induces functional resilience to sleep restriction in rats.

Study Objectives: Sleep restriction (SR) leads to performance decrements across cognitive domains but underlying mechanisms remain largely unknown. The impact of SR on performance in rodents is often assessed using tasks in which food is the reward. Investigating how the drives of hunger and sleep interact to modulate performance may provide insights into mechanisms underlying sleep loss-related performance decrements.

Pharmacological Modulation of Sleep Homeostasis in Rat: Novel Effects of an mGluR2/3 Antagonist.

Increasing vigilance without incurring the negative consequences of extended wakefulness such as daytime sleepiness and cognitive impairment is a major challenge in treating many sleep disorders. The present work compares two closely related mGluR2/3 antagonists LY3020371 and LY341495 with two well-known wake-promoting compounds caffeine and d-amphetamine. Sleep homeostasis properties were explored in male Wistar rats by manipulating levels of wakefulness via (1) physiological sleep restriction (SR), (2) pharmacological action, or (3) a combination of these.

Disturbances of sleep quality, timing and structure and their relationship with other neuropsychiatric symptoms in Alzheimer's disease and schizophrenia: Insights from studies in patient populations and animal models.

The high prevalence of sleep disturbance in neurodegenerative and psychiatric conditions is often interpreted as evidence for both sleep's sensitivity to and causal involvement in brain pathology. Nevertheless, how and which aspects of sleep contribute to brain function remains largely unknown. This review provides a critical evaluation of clinical and animal literature describing sleep and circadian disturbances in two distinct conditions and animal models thereof: Alzheimer's disease (AD) and schizophrenia.

Modelling maintenance of wakefulness in rats: comparing potential non-invasive sleep-restriction methods and their effects on sleep and attentional performance.

While several methods have been used to restrict the sleep of experimental animals, it is often unclear whether these different forms of sleep restriction have comparable effects on sleep-wake architecture or functional capacity. The present study compared four models of sleep restriction, using enforced wakefulness by rotation of cylindrical home cages over 11 h in male Wistar rats. These included an electroencephalographic-driven 'Biofeedback' method and three non-invasive methods where rotation was triggered according to a 'Constant', 'Decreasing' or random protocol based upon the 'Weibull' distribution fit to an archival Biofeedback dataset.

Phosphodiesterase 10A inhibitor, MP-10 (PF-2545920), produces greater induction of c-Fos in dopamine D2 neurons than in D1 neurons in the neostriatum.

Studies described here tested the hypothesis that phosphodiesterase 10A inhibition by a selective antagonist, MP-10, activates the dopamine D2 receptor expressing medium spiny neurons to a greater extent than the D1 receptor expressing neurons. We used regional pattern of c-Fos induction in the neostriatal subregions of rodents and direct assessment of D1-positive and -negative neurons in the DRd1a-tdTomato mice for the purpose. MP-10 (1, 3, 10 or 30 mg/kg, PO) dose-dependently increased c-Fos immunopositive nuclei in all regions of neostriatum.

Distinct pro-vigilant profile induced in rats by the mGluR5 potentiator LSN2814617.

While treatment options are available, excessive daytime sleepiness (EDS) remains a significant unmet medical need for many patients. Relatively little rodent behavioural pharmacology has been conducted in this context to assess potential pro-vigilant compounds for their ability to restore functional capacity following experimentally induced sleep loss. Male Wistar rats were prepared for electroencephalographic (EEG) recording and subject to 11 h of sleep restriction using a biofeedback-induced cage rotation protocol.

Phenotypic characterization of nonsocial behavioral impairment in neurexin 1α knockout rats.

Neurexins are neuronal presynaptic proteins that play a key role in mediation of synapse formation. Heterozygous partial deletions in the neurexin-1 gene (NRXN1, 2p16.3) have been observed in autism spectrum disorder (ASD) patients.

Corticosterone urinalysis and nicotinic receptor modulation in rats.

A routine method of measuring circulating corticosterone (CORT) levels in rats involves sampling of plasma from cannulated animals. However, being somewhat invasive, this method can potentially be confounded by its inherently stressful nature. This study investigated the feasibility of measuring corticosterone using a non-invasive sampling method from voided urine of male rats.

Diverse and often opposite behavioural effects of NMDA receptor antagonists in rats: implications for "NMDA antagonist modelling" of schizophrenia.

Rationale: Little attention has been paid to the relative equivalence of behavioural effects of NMDA receptor antagonists in rodents, with different compounds often used interchangeably to "model" aspects of schizophrenia in preclinical studies.

Objectives: To further resolve such conjecture, the present study systematically compared eight different NMDA receptor antagonists: MK-801, PCP, ketamine, memantine, SDZ 220,581, Ro 25-6981, CP 101-606 and NVP-AAM077, in a series of variable interval (VI) schedules of reinforcement. Aspects of motivation as indexed in these tasks may well be impaired in schizophrenia and undoubtedly impact on the capacity to perform more complex, explicit tasks of cognition.