Synapse
In Parkinson's disease (PD), the long term use of L‐DOPA results in major adverse effects including dyskinesia or abnormal involuntary movements. The present study focuses on the effect of the selective α1 adrenoceptor antagonist HEAT (2‐[[β‐(‐4‐hydroxyphenyl)ethyl]aminomethyl]‐1‐tetralone) in the 6‐hydroxydopamine rat model of L‐DOPA‐induced dyskinesia. We demonstrate that the selective α1 adrenoceptor...
A panel of structurally related substituted 4‐phenylpiperazines with nanomolar affinity and selectivity at D3 dopamine receptors has been synthesized. Compounds in which a heterocyclic (2‐phenyl pyridyl, 3‐phenyl pyridyl, benzothiophene, or benzofuran) moiety is adjacent to the amide was varied and/or a double bond (trans‐butenyl) replaced the four‐carbon aliphatic chain linking the arylamide with...
Small animal positron emission tomography (PET) imaging allows in vivo quantification of lesion‐ or treatment‐induced neurochemical changes in animal models of disease. Important for quantification are the kinetic modeling methods used to determine biologically‐relevant parameters of tracer‐tissue interaction. In this work, we evaluate modeling algorithms for the dopaminergic tracers 11C‐dihydrotetrabenazine...
The 5‐hydroxytryptamine system is thought to play a crucial role in the pathophysiology of depression and represents the target for selective 5‐HT reuptake inhibitors (SSRIs). Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were bred from Sprague‐Dawley (SPD) rats to produce strains with increased (FSL) or decreased (FRL) sensitivity to the cholinesterase inhibitor. The FSL rats...
The basis of neuronal vulnerability, degeneration, and sparing in PD are unknown, but there is increasing evidence to suggest that the ubiquitin‐proteasome system (UPS) plays an important role in the pathogenesis of the disorder. In this study, we employed an immunocytochemical approach to determine if the differential expression of key UPS components in various brain regions and cells might underlie...
The serotonergic system has close interactions with the dopaminergic system and is strongly implicated in the pathophysiological mechanisms and therapeutic paradigms of Parkinson's disease (PD). This study aims to investigate regional changes in 5‐hydroxytryptamine (5‐HT) 2A receptors in the rat brain 3 weeks after unilateral medial forebrain bundle lesion by 6‐hydroxydopamine (6‐OHDA). 5‐HT 2A receptor...
The reinforcing properties of cocaine have been related to increased extracellular concentrations of dopamine in the nucleus accumbens (NAc). M5 muscarinic acetylcholine receptors (mAChRs) on dopamine cells in the ventral tegmental area (VTA) facilitate mesoaccumbens dopamine transmission and are critically involved in mediating natural and drug reinforcement. We investigated the effects of pharmacological...
Exposure of the developing brain to a wide variety of drugs of abuse (e.g., stimulants, opioids, ethanol, etc.) can induce life‐long changes in behavior and neural circuitry. However, the long‐term effects of exposure to therapeutic, psychotropic drugs have only recently begun to be appreciated. Antipsychotic drugs are little studied in this regard. Here, we quantitatively analyzed dendritic architecture...
[11C]MP4A is an established radioprobe for quantification of cerebral acetylcholinesterase (AChE) activity by positron emission tomography (PET) based on the kinetics of AChE‐mediated metabolism and metabolite trapping. It has been used to assess the deficiency in cholinergic innervation in the brain of patients with dementia. Because 18F has a longer half‐life than 11C, 18F‐labeled derivatives of...
GABAB receptors (R) are widely expressed and distributed in the nervous system, and have been implicated in variety of neurodegenerative and pathophysiological disorders. However, the exact molecular mechanism regarding responsibility of GABAB1R in downstream signaling pathway is not well understood. The present study was undertaken to explore the downstream signaling and role of GABAB1R upon acute...
We previously showed that 5‐HT3 receptors are involved in the development and expression of methamphetamine (MAP)‐induced locomotor sensitization in mice. Here, we examined whether the dopaminergic or the GABAergic systems areinvolved in the attenuating effects of the 5‐HT3 receptor antagonist MDL72222 on MAP‐induced locomotor sensitization. Quantitative autoradiography of D1 ([3H]SCH23390), D2 ([...
[11C]‐(+)‐PHNO is a new dopamine D2/3 receptor agonist radiotracer which has been successfully used to measure D2/3 receptor availability in experimental animals and man. Here we report in vivo evaluation in the rat of the biodistribution, metabolism, specificity, selectivity, and dopamine sensitivity of carbon11‐labeled PHNO ([11C]‐3‐PHNO) produced by an alternative radiochemical synthesis method...
Aim. Molecular imaging studies with benzamide radioligands can reveal competition from endogenous binding at D2/3‐receptors in living brain. However, single photon emission computed tomography (SPECT) methods suffer from limited spatial resolution, and [11C]‐labeled ligands are only available at positron emission tomography (PET) research sites with cyclotron‐radiochemistry facilities, whereas [18...
Neonatal quinpirole treatment to rats produces long‐term increases in D2 receptor sensitivity that persists throughout the animal's lifetime, a phenomenon referred to as D2 priming. Male and female Sprague‐dawley rats were administered quinpirole (1 mg kg−1) or saline from postnatal days (P)1–11. At P60, all animals were given an injection of quinpirole (100 μg kg−1), and results showed that rats...
Neuronal membrane gangliosides, forming a large family of sialylated glycosphingolipids, have been hypothesized to play important roles in synaptic transmission. We studied the ex vivo electrophysiological function of neuromuscular junctions of GM2/GD2‐synthase*GD3‐synthase compound null‐mutant mice after acute removal of GM3, the only remaining ganglioside in this mouse, by in vitro treatment with...
The basal (constitutive) activity of G protein‐coupled receptors allows for the measurement of inverse agonist activity. Some competitive antagonists turn into inverse agonists under conditions where receptors are constitutively active. In contrast, neutral antagonists have no inverse agonist activity, and they block both agonist and inverse agonist activity. The μ‐opioid receptor (MOR) demonstrates...
Neural plasticity in the gustatory area of the insular cortex (IC) plays a critical role in detecting novel taste and taste memory formation, which require extracellular signal‐regulated kinase 1‐2 (ERK1‐2) phosphorylation. However, the distribution patterns of phosphorylated ERK1‐2 (pERK) responses to gustatory stimulation remain unknown. This study examined distribution patterns of gustatory stimulation‐driven...
Opioids have been demonstrated to play an important role in CNS development by affecting proliferation and differentiation in various types of neural cells. This study examined the effect of a stable delta opioid peptide [D‐Ala(2), D‐Leu(5)]‐enkephalin (DADLE) on proliferation and differentiation in an AF5 CNS neural progenitor cell line derived from rat mesencephalic cells. DADLE (1 pM, 0.1 nM, or...
Rhythmic oscillatory activities at the theta frequency (3–12 Hz) have long attracted attention, as they have been implicated in diverse brain functions. There are two kinds of hippocampal theta rhythms: Type 1 is an atropine‐resistant noncholinergic theta rhythm, and Type 2 is an atropine‐sensitive cholinergic theta rhythm. However, it has not yet been determined whether the theta rhythm generated...