Synapse
Amphetamine (AMPH) is used to treat attention deficit and hyperactivity disorders, but it can produce neurotoxicity and adverse vascular effects at high doses. The endoplasmic reticulum (ER) stress response (ERSR) entails the unfolded protein response, which helps to avoid or minimize ER dysfunction. ERSR is often associated with toxicities resulting from the accumulation of unfolded or misfolded...
The common marmoset (Callithrix jacchus) is unique among the primates in its small body size, reproductive efficacy, and characteristic social behavior, making it useful as an animal model in neuroscientific research. To assess the brain serotonergic systems, we investigated the binding of [11C]‐3‐amino‐4‐(2‐dimetylaminomethyl‐phenylsulfanyl)‐benzonitrile ([11C]DASB) to brain serotonin transporter...
High levels of anandamide are located in the basal ganglia. The subthalamic nucleus (STN) is considered to be an important modulator of basal ganglia output. The present study aims at characterizing the modulation of the electrical activity of STN neurons by exogenous anandamide or endocannabinoids. Single‐unit extracellular recordings in anesthetized rats and patch‐clamp techniques in rat brain slices...
Orofacial movements are regulated by D1‐like dopamine receptors interacting with additional mechanisms. Phospholipase C‐related catalytically inactive protein (PRIP) regulates cell surface expression of GABAA receptors containing a γ2 subunit. Mutant mice with double knockout of PRIP‐1 and PRIP‐2 were used to investigate aspects of GABAergic regulation of orofacial movements and interactions with...
Little is known regarding the involvement of the ventral pallidum (VP) in cocaine‐seeking behavior, in contrast with considerable documentation of the involvement of its major afferent, the nucleus accumbens, over the past thirty years utilizing electrophysiology, lesion, inactivation, molecular, imaging, and other approaches. The VP is neuroanatomically positioned to integrate signals projected from...
In vitro, D2 dopamine receptors (DAR) can exist in low‐ and high‐affinity states for agonists and increases of D2 receptors in high‐affinity state have been proposed to underlie DA receptor supersensitivity in vivo. Deletion of the gene for dopamine β‐hydroxylase (DBH) causes mice to become hypersensitive to the effects of psychostimulants, and in vitro radioligand binding results suggest an increased...
Ethanol associated behaviors have been linked to the β2‐subunit containing nicotinic acetylcholine receptors (β2*‐nAChR); however, there is conflicting evidence on ethanol‐induced changes in nAChR expression during and after chronic ethanol consumption. In this study, five male animals orally self‐administered ethanol for 18 ± 1 weeks. Animals were scanned with [123I]5‐IA‐85380 and SPECT prior to...
Neuropeptide FF (NPFF) is a neurotransmitter known to modulate opioid‐induced analgesia, sensitization, and reward. The expression of the immediate early gene c‐Fos was analyzed to map the distribution of neurons whose activity is regulated by central administration of the NPFF2‐selective agonist dNPA in naive mice and in animals who had received a systemic injection of morphine. The number of c‐Fos...
In young adult rats, unilateral lesions of the sensorimotor cortex lead to neuronal structural plasticity and synaptogenesis in the contralateral motor cortex, which is connected to the lesion site by transcallosal fibers. The contralesional neural plasticity varies with lesion size and results from the convergence of denervation‐induced reactive plasticity and behavioral asymmetries. It was unknown...
A variety of mechanisms that contribute to the accumulation of age‐related damage and the resulting brain dysfunction have been identified. Recently, decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age‐related brain dysfunction. However, the molecular mechanism of decreased neurogenesis with aging is still unclear. In the present study, we investigated whether...
The cerebral frontal cortex of patients who had schizophrenia shows elevated levels of RNA for calcium/calmodulin‐dependent protein kinase II beta (CaMKIIβ). In addition, recent research shows that animal models for schizophrenia, such as amphetamine‐sensitized rats, consistently show elevated levels of D2 receptors in their high‐affinity state (D2High), the major target for antipsychotic medication...
β‐Amyloid accumulation is associated with the pathogenesis of Alzheimer's disease (AD). AZD2184, a new radioligand for high‐contrast positron emission tomography (PET) imaging of Aβ‐deposits, has recently been developed and characterized in vitro and in rodents ex vivo. The objective of this study was to label AZD2184 with carbon‐11, to perform in vivo characterization of [11C]AZD2184 ([11C]5) in...
This study investigated the dendritic morphology of neurons located in the right and left basolateral amygdala (BLA) and infralimbic (IL) cortex following chronic nicotine exposure during adolescence or adulthood. Sprague–Dawley rats were administered subcutaneous injections of nicotine (0.5 mg/kg; free base) or saline three times per week for 2 weeks (six total injections). The dose period began...
Methamphetamine (MA) is widely abused and implicated in residual cognitive deficits. In rats, increases in plasma corticosterone and egocentric learning deficits are observed after a 1‐day binge regimen of MA (10 mg/kg × 4 at 2‐h intervals). The purpose of this experiment was to determine if adrenal inactivation during and following MA exposure would attenuate the egocentric learning deficits in the...
PC12 cells have been used as a model of sympathetic neurons. Nerve growth factor (NGF), basic fibroblast growth factor (bFGF), and cAMP induce neurite outgrowth from PC12 cells. cAMP induced a greater number of neurites than did NGF. In particular, we attempted to elucidate whether PC12 cell neurites, induced by several factors including NGF, bFGF, and cAMP, form synapses, and whether each neurite...
In Alzheimer's disease brains, morphological changes in the dendrites of pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been observed. These changes are particularly reflected in the decrement of both the dendritic tree and spine number. Donepezil is a potent and selective acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease. We have studied the effect...
Hippocampus is a limbic structure that participates in learning and memory formation. Specifically the dentate gyrus has been described as a hippocampal subregion with high rates of plasticity and it is targeted by different psychoactive drugs modulating synaptic plasticity. Repeated cocaine administration induces sensitization to the locomotor effects and it is believed that sensitization involves...
The protective actions of estrogen have been well evaluated in various models of neurodegeneration. These neuroprotective mechanisms may include a direct neuronal antiapoptotic effect as estrogen modulates actions of key regulators of the mitochondrial/intrinsic apoptotic cascade. We tested the ability of estrogen to protect against apoptotic signaling in cortical cell cultures exposed to Tat 1‐86...
Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N‐methyl‐11C]vorozole, we characterized the tracer distribution and kinetics in the living human brain...
Prior work indicated that serotonin transporter (SERT) inhibitors competitively inhibit substrate‐induced [3H]5‐HT release, producing rightward shifts in the substrate‐dose response curve and increasing the EC50 value without altering the Emax. We hypothesized that this finding would not generalize across a number of SERT inhibitors and substrates, and that the functional dissociation constant (Ke)...