Implementation of an antibody characterization procedure and application to the major ALS/FTD disease gene C9ORF72.

Antibodies are a key resource in biomedical research yet there are no community-accepted standards to rigorously characterize their quality. Here we develop a procedure to validate pre-existing antibodies. Human cell lines with high expression of a target, determined through a proteomics database, are modified with CRISPR/Cas9 to knockout (KO) the corresponding gene.

Optogenetic Activation of a Lateral Hypothalamic-Ventral Tegmental Drive-Reward Pathway.

Electrical stimulation of the lateral hypothalamus can motivate feeding or can serve as a reward in its own right. It remains unclear whether the same or independent but anatomically overlapping circuitries mediate the two effects. Electrical stimulation findings implicate medial forebrain bundle (MFB) fibers of passage in both effects, and optogenetic studies confirm a contribution from fibers originating in the lateral hypothalamic area and projecting to or through the ventral tegmental area.

Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens.

Excitatory afferents to the nucleus accumbens (NAc) are thought to facilitate reward seeking by encoding reward-associated cues. Selective activation of different glutamatergic inputs to the NAc can produce divergent physiological and behavioral responses, but mechanistic explanations for these pathway-specific effects are lacking. Here, we compared the innervation patterns and synaptic properties of ventral hippocampus, basolateral amygdala, and prefrontal cortex input to the NAc.

Evidence that the reward attenuating effect of the D1-like antagonist, SCH-23390, is not mediated by its agonist action at the 5-HT2c receptors.

This study investigated the effect of the 5-HT2c receptor antagonist, SB-242,084, on the attenuation of brain stimulation reward by SCH-23390. An additional experiment determined the effectiveness of SB-242,084 at blocking the reward attenuating effect of 5-HT2c agonist, CP-809,101. Results show that SB-242,084 blocked the reward attenuating effect of CP-809,101 but failed to alter that of SCH-23390.

Effects of the dopamine stabilizer, OSU-6162, on brain stimulation reward and on quinpirole-induced changes in reward and locomotion.

Dysregulation of limbic dopamine (DA) neurotransmission results in abnormal positive or negative emotional states that characterize several mental disorders. Drugs that restore DA homeostasis are most likely to constitute effective treatments for such emotional disturbances. In this study, we investigated the effects of several doses of OSU-6162, a drug that belongs to a new class named "DA stabilizers", on brain stimulation reward.

Blockade of 5-HT2a receptors reduces haloperidol-induced attenuation of reward.

Previous studies have shown that effective antipsychotic medications attenuate reward, an effect that is generally attributed to their effectiveness at blocking the dopamine D2-like receptors. As blockade of the serotonin type 2a (5-HT2a) receptors is a common property of the newer antipsychotics, the present study compared the effect of haloperidol, clozapine, and M100907 (a selective 5-HT2a antagonist) and the combined effect of haloperidol and M100907 treatment on brain stimulation reward (BSR). Experiments were performed on male Sprague-Dawley rats trained to produce an operant response to obtain electrical stimulation in the lateral hypothalamus.

Increased use of antibiotics in clozapine-treated patients.

A retrospective chart review of hospitalized patients was completed to verify whether there were differences in the prescription rate of antibiotics to patients treated with clozapine. Subjects were inpatients with a diagnosis of schizophrenia or schizoaffective disorder. Charts of all patients who received clozapine for 24 consecutive months during a period of 48 consecutive months of hospitalization were selected for the study.