Background: Stress is implicated in the pathophysiology of major depression and posttraumatic stress disorder. These conditions share core features, including motivational deficits, heighted anxiety, and sleep dysregulation. Chronic stress produces these same features in rodents, with some individuals being susceptible or resilient, as seen in humans.
View Article and Find Full Text PDFStress plays a critical role in the neurobiology of mood and anxiety disorders. Sleep and circadian rhythms are affected in many of these conditions. Here we examined the effects of chronic social defeat stress (CSDS), an ethological form of stress, on sleep and circadian rhythms.
View Article and Find Full Text PDFAdeno-associated viruses and the herpes simplex virus are the two most widely used vectors for the in vivo expression of exogenous genes. Advances in the development of these vectors have enabled remarkable temporal and spatial control of gene expression. This unit provides methods for storing, delivering, and verifying expression of adeno-associated and herpes simplex viruses in the adult mouse brain.
View Article and Find Full Text PDFEnvironmentally induced relapse to cocaine seeking requires the retrieval of context-response-cocaine associative memories. These memories become labile when retrieved and must undergo reconsolidation into long-term memory storage to be maintained. Identification of the molecular underpinnings of cocaine-memory reconsolidation will likely facilitate the development of treatments that mitigate the impact of cocaine memories on relapse vulnerability.
View Article and Find Full Text PDFInt J Neuropsychopharmacol
September 2014
Despite the well-documented involvement of dopamine D1-like receptor stimulation in cocaine-induced goal-directed behaviours, little is known about the specific contribution of D1-like receptor populations in the dorsal hippocampus (DH) to drug context-induced cocaine-seeking or drug-reinforced instrumental behaviours. To investigate this question, rats were trained to lever press for un-signalled cocaine infusions in a distinct context followed by extinction training in a different context. Cocaine-seeking behaviour (non-reinforced lever responding) was then assessed in the previously cocaine-paired and extinction contexts.
View Article and Find Full Text PDFCocaine-seeking behavior triggered by drug-paired environmental context exposure is dependent on orbitofrontal cortex (OFC)-basolateral amygdala (BLA) interactions. Here, we present evidence supporting the hypothesis that dopaminergic input from the ventral tegmental area (VTA) to the OFC critically regulates these interactions. In experiment 1, we employed site-specific pharmacological manipulations to show that dopamine D1-like receptor stimulation in the OFC is required for drug context-induced reinstatement of cocaine-seeking behavior following extinction training in an alternate context.
View Article and Find Full Text PDFRationale: Contextual control over drug relapse depends on the successful reconsolidation and retention of context-response-cocaine associations in long-term memory stores. The basolateral amygdala (BLA) plays a critical role in cocaine memory reconsolidation and subsequent drug context-induced cocaine-seeking behavior; however, less is known about the cellular mechanisms of this phenomenon.
Objectives: The present study evaluated the hypothesis that protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII) activation in the BLA is necessary for the reconsolidation of context-response-cocaine memories that promote subsequent drug context-induced cocaine-seeking behavior.
Glutamatergic neurotransmission in the dorsal hippocampus (DH) is necessary for drug context-induced reinstatement of cocaine-seeking behavior in an animal model of drug relapse. Furthermore, in vitro studies suggest that the Src family of tyrosine kinases critically regulates glutamatergic cellular functions within the DH. Thus, Src-family kinases in the DH may similarly control contextual cocaine-seeking behavior.
View Article and Find Full Text PDFThe reconsolidation of cocaine memories following retrieval is necessary for the sustained ability of a cocaine-paired environmental context to elicit cocaine seeking. Extracellular signal-regulated kinase (ERK) is an intracellular signaling molecule involved in nucleus accumbens core (NACc)-mediated reconsolidation of Pavlovian cocaine memories. Here, we used a rodent model of drug context-elicited relapse to test the hypothesis that ERK would be similarly required for the reconsolidation of context-response-cocaine memories that underlie drug context-induced reinstatement of instrumental cocaine-seeking behavior, with a focus on the NACc and on the basolateral amygdala (BLA), another important locus for the reconsolidation of cocaine memories.
View Article and Find Full Text PDFRationale: Chronic cocaine exposure produces unconditioned enhancement in impulsive decision making; however, little is known about the effects of cocaine-paired conditioned stimuli on this behavior. Thus, this study explored the effects of cocaine-paired contextual stimuli on impulsive decision making and the contribution of nicotinic acetylcholine receptors (nAChRs) to this phenomenon.
Methods: Rats were trained to achieve stable performance on a delay discounting task, which involved lever press-based choice between a single food pellet (small reward) available immediately and three food pellets (large reward) available after a 10-, 20-, 40-, or 60-s time delay.
Contextual stimulus control over instrumental drug-seeking behavior relies on the reconsolidation of context-response-drug associative memories into long-term memory storage following retrieval-induced destabilization. According to previous studies, the basolateral amygdala (BLA) and dorsal hippocampus (DH) regulate cocaine-related memory reconsolidation; however, it is not known whether these brain regions interact or independently control this phenomenon. To investigate this question, rats were trained to lever press for cocaine reinforcement in a distinct environmental context followed by extinction training in a different context.
View Article and Find Full Text PDFThe functional integrity of the nucleus accumbens (NAC) core and shell is necessary for contextual cocaine-seeking behavior in the reinstatement animal model of drug relapse; however, the neuropharmacological mechanisms underlying this phenomenon are poorly understood. The present study evaluated the contribution of metabotropic glutamate receptor subtype 1 (mGluR1) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor populations to drug context-induced reinstatement of cocaine-seeking behavior. Rats were trained to lever press for un-signaled cocaine infusions in a distinct context followed by extinction training in a different context.
View Article and Find Full Text PDFThe basolateral amygdala (BLA) and lateral orbitofrontal cortex (OFC) are critical elements of the neural circuitry that regulates drug context-induced reinstatement of cocaine-seeking behavior. Given the existence of dense reciprocal anatomical connections between these brain regions, this study tested the hypothesis that serial information processing by the BLA and OFC is necessary for drug context-induced cocaine-seeking behavior. Male Sprague-Dawley rats were trained to lever press for un-signaled cocaine infusions (0.
View Article and Find Full Text PDFPrevious findings in rats suggest that the rostral basolateral amygdala (rBLA) and prelimbic prefrontal cortex (plPFC) are likely components of cue reinstatement circuitry based on bilateral inactivation of each site alone. In the present investigation, we examined whether the rBLA and plPFC interact to regulate reinstatement of cocaine-seeking behavior elicited by reexposure to a combination of discrete and contextual cocaine-paired cues. After establishing stable baseline responding under a second-order schedule of cocaine reinforcement and cue presentation, rats underwent response-extinction training in which cocaine and cocaine-paired cues were withheld.
View Article and Find Full Text PDFThe spontaneously hypertensive rat (SHR) is used as an animal model of attention deficit hyperactivity disorder (ADHD). It displays deficits in frontostriatal functioning, but it is unclear if medial temporal lobe functioning and structure are affected. We used behavioral tasks that evaluate functioning of the amygdala and hippocampus to compare male SHR to male rats from two inbred comparator strains, the normotensive Wistar-Kyoto (WKY) and the hypertensive Wistar-Kyoto (WKHT) rat (n = 8/strain).
View Article and Find Full Text PDFSemin Respir Crit Care Med
June 2009
Central congenital hypoventilation syndrome (CCHS) is a disorder in which affected individuals fail to breathe during sleep despite progressive hypercapnia and hypoxia. Discovery of the genetic link between PHOX2B gene mutations and CCHS represents a breakthrough in the diagnosis of CCHS, identification of patients with late-onset central hyperventilation syndrome (LO-CHS), association of mutated alleles with disease severity, and clues to the pathophysiology responsible for the disorder. CCHS is a neurocristopathy, and affected individuals are more likely to have disorders of the autonomic nervous system, Hirschsprung disease, and neural crest tumors.
View Article and Find Full Text PDFThe epithelial surface is often proposed to actively participate in host defense, but evidence that this is the case remains circumstantial. Similarly, respiratory paramyxoviral infections are a leading cause of serious respiratory disease, but the basis for host defense against severe illness is uncertain. Here we use a common mouse paramyxovirus (Sendai virus) to show that a prominent early event in respiratory paramyxoviral infection is activation of the IFN-signaling protein Stat1 in airway epithelial cells.
View Article and Find Full Text PDFMore than 1300 lung or heart-lung transplants have been performed in children to date, resulting in many years of improved quality of life. Increasing experience has demonstrated that this therapy is unique and differs from adult lung transplantation in terms of indications, complications, pharmacokinetics, and monitoring. Unlike adult lung transplant recipients, cystic fibrosis and pulmonary vascular disease are very common indications.
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