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Animal models provide compelling evidence that chronic stress is associated with biochemical and morphological changes in the brain, many of which are mediated by corticosterone, a principal glucocorticoid synthesized in the rodent adrenal cortex and secreted in response to stress. To better characterize the effects of chronic corticosterone at the synaptic and subsynaptic level, we implanted three‐month‐old...
It has been shown that atypical antipsychotics significantly reduce smoking and alcohol consumption in schizophrenic patients. However, our knowledge about the effect of risperidone, especially on nicotine abuse is limited. We aimed to test the effects of risperidone in an animal model of nicotine‐induced locomotor sensitization, which represents initial neuroadaptations and continued behavioral changes...
Quantitative interpretation of brain [18F]FDOPA PET data has been made possible by several kinetic modeling approaches, which are based on different assumptions about complex [18F]FDOPA metabolic pathways in brain tissue. Simple kinetic macro parameters are often utilized to quantitatively evaluate metabolic and physiological processes of interest, which may include DDC activity, vesicular storage,...
Modafinil, a psychostimulant, is used in the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea. Preclinical and clinical studies suggest that modafinil may have reinforcing effects. However, a possible rewarding property of modafinil has not been fully investigated. In this study, we assessed the potential rewarding property...
[3H]CUMI‐101 is a 5‐HT1A partial agonist, which has been evaluated for use as a positron emission tracer in baboon and humans. We sought to evaluate the properties of [3H]CUMI‐101 ex vivo in awake rats and determine if [3H]CUMI‐101 can measure changes in synaptic levels of serotonin after different challenge paradigms. [3H]CUMI‐101 shows good uptake and good specific binding ratio (SBR) in frontal...
Ventral tegmental area (VTA) GABA neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in alcohol reward. The aim of this study was to examine the role of midbrain connexin‐36 (Cx36) gap junctions (GJs) in ethanol intoxication and consumption. Using behavioral, molecular, and electrophysiological...
Connexin‐36 (Cx36) gap junctions (GJs) appear to be involved in the synchronization of GABA interneurons in many brain areas. We have previously identified a population of Cx36‐connected ventral tegmental area (VTA) GABA neurons that may regulate mesolimbic dopamine (DA) neurotransmission, a system implicated in reward from both natural behaviors and drugs of abuse. The aim of this study was to determine...
In the mammlian brain, the hippocampus has been established as a principle structure for learning and memory processes, which involve synaptic plasticity. Althought a relationship between synaptic plasticity and stimulation frequency has been reported in numerous studies, little is known about the importance of pulse number on synaptic plasticity. Here we investigated whether the pulse number can...
Cortical and striatal regions of the brain contain high levels of the cannabinoid‐1 (CB1) receptor, the central neuronal mediator of activity‐dependent synaptic plasticity evoked by endocannabinoids. The expression levels of parvalbumin, a calcium‐binding protein found in fast‐spiking interneurons of both regions, may be controlled in part by synaptic activity during critical periods of development...
In this study, we compared two different D2/3 receptor ligands, [18F]fallypride and [18F]desmethoxyfallypride ([18F]DMFP) with respect to the duration of the scan, visualization of extrastriatal receptors, and binding potentials (BPND) in the rat brain. In addition, we studied the feasibility of using these tracers following a period of awake tracer uptake, during which the animal may perform a behavioral...
Curcumin (Curcuma Longa Linn), the active component of turmeric, has been shown to be effective in ameliorating several stress and drug‐induced disorders in rats and humans. However, it is unclear whether short term curcumin administration can prevent the abnormal oro‐facial movements (AOFM) which develop following blockade of dopamine D2 receptors by antagonist such as Haloperidol. The objective...
Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH‐dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent...
A series of microPET imaging studies were conducted in anesthetized rhesus monkeys using the dopamine D3‐selective partial agonist, [18F]5. There was variable uptake in regions of brain known to express a high density of D3 receptors under baseline conditions. Pretreatment with lorazepam (1 mg/kg, i.v. 30 min) to reduce endogenous dopamine activity before tracer injection resulted in a dramatic increase...
Intractable epilepsy (IE) patients have synaptic dysfunction. However, the exact mechanism of synaptic function needs further elucidation. The aim of this study was to use immunohistochemistry, immunofluorescence, and Western blotting to investigate the expression of the Liprin‐α1 protein, one of the synapse‐associated proteins, in human IE brain tissues and experimental rats and to discuss the possible...
This in vitro study investigates and compares the effects of NK3 receptor ligands on the firing rate of rat and guinea pig midbrain dopamine neurons. The findings are discussed in the light of choosing suitable animal models for investigating pharmacological properties of NK3 receptor antagonists, which have been proposed to possess therapeutic activity in neuropsychiatric diseases like e.g. schizophrenia...
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