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Amyloid β protein (Aβ) is responsible for the deficits of learning and memory in Alzheimer's disease (AD). The high affinity between Aβ and nicotinic acetylcholine receptors (nAChRs) suggests that the impairment of cognitive function in AD might be involved in the Aβ‐induced damage of nAChRs. This study investigated the effects of Aβ fragments on nAChR‐mediated membrane currents in acutely isolated...
This study aims to investigate the pharmacokinetics of a recently developed radiotracer for imaging of the norepinephrine transporter (NET) in baboon brain, 123I‐INER, using single photon emission computed tomography (SPECT). In addition, it also aims to determine NET occupancy by atomoxetine and reboxetine, two selective norepinephrine reuptake inhibitors, using 123I‐INER in baboons. Baseline and...
Fatty acid amide hydrolase (FAAH) regulates tissue concentrations of N‐acylethanolamines (NAEs), including the endocannabinoid, N‐arachidonylethanolamide (anandamide, AEA). FAAH activity and NAEs are widely distributed throughout the brain and FAAH activity regulates an array of processes including emotion, cognition, inflammation, and feeding. However, there is relatively little research describing...
Depletion of cholinergic interneurons in the ventral striatum (nucleus accumbens or N.Acc.) in adult rats increases the locomotor activating effects of amphetamine. It also impairs sensorimotor gating processes, an effect reversed by the antipsychotic haloperidol. These behavioral effects are suggestive of pronounced hyper‐responsiveness of the mesolimbic dopamine (DA) projection to the N.Acc. However,...
Although Type 1 inositol 1,4,5‐trisphosphate receptors (IP3Rs‐1) are one of the major calcium channels to regulate intracellular Ca2+ concentration, there have been few available data how their expression is modified by long‐term exposure to ethanol. The present study attempted to clarify mechanisms of modification of IP3R‐1 expression during long‐term ethanol exposure by γ‐aminobutyric acid (GABA)A...
The competitive inhibition of dopamine transporters (DAT) with cocaine, a specific DAT inhibitor, was evaluated with a feedback‐controlled bolus plus infusion (FC‐B/I) method using animal positron emission tomography (PET) in the living brain of conscious monkey. 2β‐Carbomethoxy‐3β‐(4‐fluorophenyl)‐8‐(2‐[18F]fluoroethyl) nortropane ([18F]β‐CFT‐FE; Harada et al. [2004] Synapse 54:37–45) was used for...
The periaqueductal gray (PAG) is a critical brain region involved in opioid analgesia and provides efferents to descending pathways that modulate nociception. In addition, the PAG contains ascending pathways to regions involved in the regulation of reward, including the substantia nigra (SN) and the ventral tegmental area (VTA). SN and VTA contain dopaminergic neurons that are critical for the maintenance...
Environmental enrichment during development may reduce drug abuse liability by modulating dopamine transporter (DAT) function. Nucleus accumbens (NAc) shell and core respond differentially to regulate the rewarding properties and locomotor stimulant effects of psychostimulants. The current study evaluated dopamine (DA) clearance (CLDA) in the NAc shell and core using in vivo voltammetry in rats raised...
Brown adipose tissue (BAT) plays a significant role in metabolism. In this study, we report the use of atomoxetine (a clinically applicable norepinephrine reuptake inhibitor) for 18F‐FDG PET imaging of BAT and its effects on heat production and blood glucose concentration. Fasted‐male Sprague‐Dawley rats were administered with intravenous 18F‐FDG. The same rats were treated with atomoxetine (0.1 mg/kg,...
In this work, we analyzed the interpulse interval (IPI) of doublets and triplets in single neurons of three biological models. Pulse trains with two or three spikes originate from the process of sensory mechanotransduction in neurons of the locust femoral nerve, as well as through spontaneous activity both in the abdominal motor neurons and the caudal photoreceptor of the crayfish. We show that the...
Recent behavioral studies suggest that nonselective agonists of cannabinoid receptors may regulate serotonin 2A (5‐HT2A) receptor neurotransmission. Two cannabinoids receptors are found in brain, CB1 and CB2 receptors, but the molecular mechanism by which cannabinoid receptors would regulate 5‐HT2A receptor neurotransmission remains unknown. Interestingly, we have recently found that certain cannabinoid...
In previous studies, we have reported sex‐related differences during morphine withdrawal. We have also shown that the GABAB agonist baclofen (BAC) was able to prevent the morphine withdrawal syndrome in male as well as in female mice. Considering that early gene expression is induced by drugs of abuse, we evaluated the expression of c‐Fos in several brain areas, in mice of either sex during naloxone...
Depressive disorders and the treatment thereof have been associated with a number of neuroplastic events, such as neurogenesis and synaptic remodeling in discrete areas of the brain. The associations of these events in changes regarding the energy supply have not been investigated. Here, we investigated the changes in mitochondrial plasticity and its correlation to morphological alterations of neuroplasticity...
Ethylmalonic acid (EMA) accumulates in tissues of patients affected by short‐chain acyl‐CoA dehydrogenase deficiency and ethylmalonic encephalopathy, illnesses characterized by variable neurological symptoms. In this work, we investigated the in vitro and in vivo EMA effects on Na+,K+‐ATPase (NAK) activity and mRNA levels in cerebral cortex from 30‐day‐old rats. For in vitro studies, cerebral cortex...
The positive allosteric modulator (PAM) binding site for metabotropic glutamate receptor subtype 5 (mGlu5) lacks a readily available radio‐labeled tracer fordetailed structure‐activity studies. This communication describes a selective mGlu5 compound, 7‐methyl‐2‐(4‐(pyridin‐2‐yloxy)benzyl)‐5‐(pyridin‐3‐yl)isoindolin‐1‐one (PBPyl) that binds with high affinity to human mGlu5 and exhibits functional...
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