Search results for "Striatum"
showing 10 items of 178 documents
Occupancy of striatal D 2 -like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic
1999
Rationale: EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reported recently to have antipsychotic activity in schizophrenia. However, its metabolite, EMD 59983, binds also to D2 and D3 dopamine (DA) receptors. Objectives: The aim of this study was to test, using single photon emission computed tomography (SPECT) and [123I]iodobenzamide (IBZM) as the radiotracer, whether EMD 59983 would pass the blood-brain barrier and to what extent it would contribute to the effects of EMD 57445 in schizophrenia. Methods: Two IBZM SPECT-scans were performed in five neuroleptic-free schizophrenic patients (DSM IV), one befo…
Loss of the Ca2+/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine.
2008
The persistent nature of addiction has been associated with activity-induced plasticity of neurons within the striatum and nucleus accumbens (NAc). To identify the molecular processes leading to these adaptations, we performed Cre/loxP-mediated genetic ablations of two key regulators of gene expression in response to activity, the Ca 2+ /calmodulin-dependent protein kinase IV (CaMKIV) and its postulated main target, the cAMP-responsive element binding protein (CREB). We found that acute cocaine-induced gene expression in the striatum was largely unaffected by the loss of CaMKIV. On the behavioral level, mice lacking CaMKIV in dopaminoceptive neurons displayed increased sensitivity to cocai…
A53T-Alpha-Synuclein Overexpression Impairs Dopamine Signaling and Striatal Synaptic Plasticity in Old Mice
2010
BACKGROUND: Parkinson's disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. To characterize the progression, we employed young adult as well as old mice. Analysis of striatal neurotransmitter content demonstrated that dopamine (DA…
Opiate-induced dopamine release is modulated by severity of alcohol dependence: an [(18)F]fallypride positron emission tomography study.
2011
Background Preclinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain. Specifically, alcohol-induced release of β-endorphins stimulates μ-opioid receptors (MORs), which is believed to cause dopamine release in the brain reward system. Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol. In the present study, a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effect…
Protective action of 1,3-butanediol in cerebral ischemia. A neurologic, histologic, and metabolic study.
1987
1,3-Butanediol (BD) is converted in the body to β-hydroxybutyrate, and previous studies have shown that hyperketonemia had beneficial effects in experimental models of generalized hypoxia. The aim of this study was to determine if BD would reduce brain damage following cerebral ischemia. A transient forebrain ischemia of 30-min duration was induced by the four-vessel occlusion technique in control and BD-treated rats (25 mmol/kg, i.p.; 30 min prior to ischemia). BD treatment led to significant improvement of neurologic deficit during the 72-h recovery period and reduced neuronal damage in the striatum and cortex but not in the CA1 sector of the hippocampus. Evaluation of cerebral energy me…
Neuroprotective effect of erythropoietin and darbepoetin alfa after experimental intracerebral hemorrhage.
2009
OBJECTIVE: Intracerebral hemorrhage (ICH) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, erythropoietin (EPO) and its long-lasting analog, darbepoetin alfa, have been demonstrated to be neuroprotective in several models of neuronal insult. The objectives of this study were to analyze whether the systemic administration of recombinant human EPO (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery and brain damage in a rat model of ICH. METHODS: Experimental ICH was induced in rats by injecting autologous blood into the right striatum under stereotactic guidance. Subsequently, animal…
Cannabinoid CB1 receptors regulate neuronal TNF-α effects in experimental autoimmune encephalomyelitis.
2011
Abstract Cannabinoid CB1 receptors (CB1Rs) regulate the neurodegenerative damage of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB1R stimulation exerts protective effects is still unclear. Here we show that pharmacological activation of CB1Rs dampens the tumor necrosis factor α (TNFα)-mediated potentiation of striatal spontaneous glutamate-mediated excitatory postsynaptic currents (EPSCs), which is believed to cogently contribute to the inflammation-induced neurodegenerative damage observed in EAE mice. Furthermore, mice lacking CB1Rs showed a more severe clinical course and, in parallel, exacerbated alterations of sEPSC duration af…
Salsolinol and ethanol-derived excitation of dopamine mesolimbic neurons: new insights
2013
Evidence supporting the essential role of brain-derived ethanol metabolites in the excitation of dopamine (DA) midbrain neurons has multiplied in the last 10–15 years. The pioneer and influential behavioral studies by CM Aragon and colleagues (see Correa et al., 2012 for a complete review) and more recent data (Sanchez-Catalan et al., 2009; Marti-Prats et al., 2010, 2013) have repeatedly demonstrated the crucial role displayed by acetaldehyde (ACD) in the locomotor and other behavioral responses elicited by ethanol. Although these experiments mainly used an indirect measure (exploratory locomotion) as an index of the excitation of DA neurons in the ventral tegmental area (VTA), results stro…
The Interaction of Person-Affect-Cognition-Execution (I-PACE) model for addictive behaviors: Update, generalization to addictive behaviors beyond int…
2019
We propose an updated version of the Interaction of Person-Affect-Cognition-Execution (I-PACE) model, which we argue to be valid for several types of addictive behaviors, such as gambling, gaming, buying-shopping, and compulsive sexual behavior disorders. Based on recent empirical findings and theoretical considerations, we argue that addictive behaviors develop as a consequence of the interactions between predisposing variables, affective and cognitive responses to specific stimuli, and executive functions, such as inhibitory control and decision-making. In the process of addictive behaviors, the associations between cue-reactivity/craving and diminished inhibitory control contribute to th…
Tonically Active Neurons in the Monkey Striatum are Sensitive to Sensory Events in a Manner that Reflects their Predictability in Time
2002
It is now well established that tonically active neurons (TANs) in the monkey striatum respond to motivationally relevant sensory events, such as conditioned stimuli to which the animal had to react correctly to obtain reward. Recent findings obtained in our laboratory suggested that stimulus prediction may influence the responsiveness of the TANs. In the present study we specifically investigated the effects of temporal aspects of prediction on the responses of single TANs recorded both in the caudate nucleus and putamen of two macaque monkeys. Three different behavioral situations were employed: (1) an instrumental task, in which a visual stimulus triggering a rewarded movement was preced…