Diminished Myoinositol in Ventromedial Prefrontal Cortex Modulates the Endophenotype of Impulsivity.

Maladaptive impulsivity manifests in a variety of disorders, including attention-deficit hyperactivity disorder (ADHD), depression, and substance use disorder. However, the etiological mechanisms of impulsivity remain poorly understood. In the present study, we used in-vivo proton magnetic resonance spectroscopy (1H-MRS) to investigate neurometabolite content in the prefrontal cortex (PFC) and striatum of rats exhibiting low- versus high-impulsive (LI, HI) behavior on a visual attentional task.

Ventral Striatal D2/3 Receptor Availability Is Associated with Impulsive Choice Behavior As Well As Limbic Corticostriatal Connectivity.

Background: Low dopamine D2/3 receptor availability in the nucleus accumbens shell is associated with highly impulsive behavior in rats as measured by premature responses in a cued attentional task. However, it is unclear whether dopamine D2/3 receptor availability in the nucleus accumbens is equally linked to intolerance for delayed rewards, a related form of impulsivity.

Methods: We investigated the relationship between D2/3 receptor availability in the nucleus accumbens and impulsivity in a delay-discounting task where animals must choose between immediate, small-magnitude rewards and delayed, larger-magnitude rewards.

Differences in trait impulsivity do not bias the response to pharmacological drug challenge in the rat five-choice serial reaction time task.

Rationale: Maladaptive impulsivity is symptomatic of several neuropsychiatric disorders including schizophrenia, attention-deficit hyperactivity disorder (ADHD), and substance abuse disorders; paradigms designed to assess the underlying neurobiology of this behavior are essential for the discovery of novel therapeutic agents. Various models may be used to assess impulsivity as measured by the five-choice serial reaction time task (5-CSRTT), including variable inter-trial interval (ITI) sessions, the selection of extreme high and low impulsivity phenotypes from a large outbred population of rats, as well as pharmacological challenges.

Objectives: The aim of this study is to evaluate if pharmacological challenge models for impulsivity are biased by underlying differences in impulsivity phenotype.

Markers of serotonergic function in the orbitofrontal cortex and dorsal raphé nucleus predict individual variation in spatial-discrimination serial reversal learning.

Dysfunction of the orbitofrontal cortex (OFC) impairs the ability of individuals to flexibly adapt behavior to changing stimulus-reward (S-R) contingencies. Impaired flexibility also results from interventions that alter serotonin (5-HT) and dopamine (DA) transmission in the OFC and dorsomedial striatum (DMS). However, it is unclear whether similar mechanisms underpin naturally occurring variations in behavioral flexibility.

Selective effects of insecticides on nigrostriatal dopaminergic nerve pathways.

A degeneration of the nigrostriatal pathway is a primary component of Parkinson's disease (PD), and we have investigated the actions of insecticides on this pathway. For in vivo exposures, C57BL/6 mice were treated three times over a 2-week period with heptachlor, the pyrethroids deltamethrin and permethrin, or chlorpyrifos. One day after the last treatment, we observed that heptachlor and the pyrethroids increased maximal [3H]dopamine uptake in striatal synaptosomes from treated mice, with dose-dependent changes in Vmax displaying a bell-shaped curve.

Discovery of non-zwitterionic GABA(A) receptor full agonists and a superagonist.

Numerous previous studies of GABA(A) receptor ligands have suggested that GABA(A) receptor agonists must be zwitterionic and feature an intercharge separation similar to that of GABA (approx. 4.7-6A).

Selective effects of cyclodiene insecticides on dopamine release in mammalian synaptosomes.

Cyclodiene insecticides release labeled neurotransmitter in striatal and cortical synaptosome preparations under nondepolarizing conditions, typically showing half-maximal potencies for release in the low micromolar range. This level of potency is similar to those reported for inhibition of 36Cl- influx at the gamma-aminobutyric acid (GABA)(A) receptor, their consensus target site. A wide variety of other GABA(A) antagonists, including picrotoxinin and bicuculline, did not cause significant dopamine release, which obviated direct involvement of the GABA(A) receptor as a possible site of action.