Psychomotor stimulants and neuroleptics exert multiple effects on dopaminergic signaling and produce the dopamine (DA)-related behaviors of motor activation and catalepsy, respectively. However, a clear relationship between dopaminergic activity and behavior has been very difficult to demonstrate in the awake animal, thus challenging existing notions about the mechanism of these drugs. The pres...

gamma-Hydroxybutyrate (GHB), a therapeutic for narcolepsy and a drug of abuse, has several mechanisms of action that involve GHB and GABA(B) receptors, metabolism to GABA, and modulation of dopaminergic signaling. The aim of these studies was to examine the role of GHB and GABA(B) receptors in the behavioral effects of GHB. Three approaches were used to synthesize GHB analogs that bind selectiv...

INTRODUCTION This paper describes narcolepsy with cataplexy in two monozygotic twin sisters. OBJECTIVE To clinically illustrate the involvement of neurological, genetic and immunologic systems in narcolepsy. MATERIAL AND METHODS We performed a restropective study of these patients that were followed in the sleep medicine ambulatory clinic of the Faculdade de Medicina de Ribeirao Preto. RE...

In cataleptic clinging, produced either by catecholamine-blocking drugs or lateral hypothalamic damage in adult cats, rats, or monkeys, bandaging the face and neck causes the head to fall backwards. Early in development, a similar reaction can be seen in normal undrugged infants.

A study by Zhang et al. in this issue of Neuron reveals a novel mechanism of control of vestibular motor functions by the orexin (hypocretin) system in the perifornical/LH area through the lateral vestibular nucleus in the brainstem. This knowledge provides new insights into the understanding of brain circuitry that controls motor functions and diseases/conditions related to impairments in this...

We performed short-term bi-directional selective breeding for haloperidol-induced catalepsy, starting from three mouse populations of increasingly complex genetic structure: an F2 intercross, a heterogeneous stock (HS) formed by crossing four inbred strains (HS4) and a heterogeneous stock (HS-CC) formed from the inbred strain founders of the Collaborative Cross (CC). All three selections were s...

Non-dopaminergic drugs acting either on adenosine A2A or metabotropic glutamate (mGlu) receptors reduce motor impairment in animal models of Parkinson's disease (PD), suggesting a possible functional interaction between these receptors to regulate basal ganglia function. The present study therefore tested the behavioural effects of compounds acting selectively on A2A or on specific mGlu recepto...

A duplexed, functional multiaddition high throughput screen and subsequent iterative parallel synthesis effort identified the first highly selective and CNS penetrant glucagon-like peptide-1R (GLP-1R) positive allosteric modulator (PAM). PAM (S)-9b potentiated low-dose exenatide to augment insulin secretion in primary mouse pancreatic islets, and (S)-9b alone was effective in potentiating endog...