Opioidergic system and N-methyl D-aspartate receptor (NMDA-R) hypofunction: Translational implications for the pathophysiology of psychosis and drug addiction

2011 ◽  
Vol 26 (S2) ◽  
pp. 1231-1231
Author(s):  
E.F. Buonaguro ◽  
F. Marmo ◽  
L. Avvisati ◽  
G. Latte ◽  
R. Rossi ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Drugs Of Abuse ◽  
Premotor Cortex ◽  
Region Of Interest ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Preclinical Model ◽  
Sprague Dawley ◽  
Somatosensory Cortices ◽  
Sprague Dawley Rats

Enkephalin is an opioidergic neuromodulator that has been implicated in long-term behavioural sensitization after administration of drugs of abuse. Enkephalin is also a molecular marker of GABAergic neurons in the striato-pallidal pathway that is involved in sensory-motor gating and has been considered dysfunctional in the pathophysiology of psychosis.In this study we investigated in male Sprague Dawley rats putative changes in Enkephalin transcripts by in situ hybridization after acute or subchronic administration of ketamine in either high or low subanaesthetic doses (50 mg/kg and 12 mg/kg respectively). Ketamine is a non-competitive NMDA-R antagonist that perturbs glutamate neurotransmission and provides a preclinical model of psychosis-like behaviour in rats.In the acute paradigm the expression of Enkephalin was reduced in the motor, premotor, somatosensory cortices as well as in anterior cingulate. In the subchronic paradigm Enkephalin expression was reduced in the premotor cortex, in the ventromedial caudate-putamen and in the shell of nucleus accumbens. Comparative analysis showed that the relative decrement in gene expression was not significantly different between the acute and subchronic paradigm for each region of interest.Changes in distribution of Enkephalin expression and correlation analysis of functionally related brain regions suggest that Enkephalin transcripts reduction may be implicated in the motivational aspects of drug addiction and may help explaining some aspects of the pathophysiology in ketamine-induced psychosis.

Enzymatic condensation of dopamine and acetaldehyde: a salsolinol synthase from rat brain

Biologia ◽  
2011 ◽  
Vol 66 (6) ◽  
Author(s):  
Xuechai Chen ◽  
Abida Arshad ◽  
Hong Qing ◽  
Rui Wang ◽  
Jianqing Lu ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Substantia Nigra ◽  
Human Subjects ◽  
Enzymatic Reaction ◽  
Brain Regions ◽  
Activity Detection ◽  
Reaction Products ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Salsolinol Synthase

AbstractSalsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; Sal) is structurally similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which is supposed to have a role in the development of Parkinson-like syndrome in both human and non-human subjects. In the human brain, the amount of (R)-enantiomer of Sal is much higher than (S)-enantiomer, suggesting that a putative enzyme may participate in the synthesis of (R)-salsolinol, called (R)-salsolinol synthase. In this study, the (R)-salsolinol synthase activity in the condensation of dopamine and acetaldehyde was investigated in the crude extracts from the brains of Sprague Dawley rats. Identification of the enzymatic reaction products and enzyme activity detection were achieved by HPLC-electrochemical detection. The discovery of this enzyme activity in rat’s brain indicates the natural existence of (R)-salsolinol synthase in the brains of humans and rats, and it is distributed in most brain regions of rat with higher activity in soluble proteins extracted from striatum and substantia nigra.

Cardiovascular and renal sympathetic activation by blood-borne TNF-α in rat: the role of central prostaglandins

2003 ◽  
Vol 284 (4) ◽  
pp. R916-R927 ◽  
Author(s):  
Zhi-Hua Zhang ◽  
Shun-Guang Wei ◽  
Joseph Francis ◽  
Robert B. Felder
Keyword(s):  
Lateral Ventricle ◽  
Biological Effects ◽  
Brain Regions ◽  
Ventrolateral Medulla ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Hypothalamic Level ◽  
Renal Sympathetic

In pathophysiological conditions, increased blood-borne TNF-α induces a broad range of biological effects, including activation of the hypothalamic-pituitary-adrenal axis and sympathetic drive. In urethane-anesthetized adult Sprague-Dawley rats, we examined the mechanisms by which blood-borne TNF-α activates neurons in paraventricular nucleus (PVN) of hypothalamus and rostral ventrolateral medulla (RVLM), two critical brain regions regulating sympathetic drive in normal and pathophysiological conditions. TNF-α (0.5 μg/kg), administered intravenously or into ipsilateral carotid artery (ICA), activated PVN and RLVM neurons and increased sympathetic nerve activity, arterial pressure, and heart rate. Responses to intravenous TNF-α were not affected by vagotomy but were reduced by mid-collicular decerebration. Responses to ICA TNF-α were substantially reduced by injection of the cyclooxygenase inhibitor ketorolac (150 μg) into lateral ventricle. Injection of PGE2 (50 ng) into lateral ventricle or directly into PVN increased PVN or RVLM activity, respectively, and sympathetic drive, with shorter onset latency than blood-borne TNF-α. These findings suggest that blood-borne cytokines stimulate cardiovascular and renal sympathetic responses via a prostaglandin-dependent mechanism operating at the hypothalamic level.

Subfornical organ and supraoptic nucleus connections with septal neurons in rats

1985 ◽  
Vol 249 (2) ◽  
pp. R214-R218 ◽  
Author(s):  
A. V. Ferguson ◽  
C. W. Bourque ◽  
L. P. Renaud
Keyword(s):  
Supraoptic Nucleus ◽  
Medial Septum ◽  
Brain Regions ◽  
Subfornical Organ ◽  
Sprague Dawley ◽  
Indirect Pathway ◽  
Antidromic Activation ◽  
Diagonal Band ◽  
Sprague Dawley Rats ◽  
Septal Neurons

Extracellular single unit recordings obtained in pentobarbital-anesthetized male Sprague Dawley rats were utilized to examine the electrophysiology of connections of medial septum-diagonal band of Broca (MS-DBB) neurons with the subfornical organ (SFO), hippocampal commissure (HC), and supraoptic nucleus (SON). Of the 119/216 cells tested that demonstrated antidromic activation from SON, many (60%) were orthodromically excited by SFO stimulation, whereas most (68%) were unresponsive to stimulation in the adjacent HC. Separate populations of MS-DBB neurons that displayed antidromic activation from the SFO (11/140 cells tested) or HC (24/78 tested) were orthodromically excited by SON stimulation. Three cells were activated antidromically from both the SFO and SON. These observations reveal some possible interconnections between these three brain regions and point to the existence of an indirect pathway whereby the SFO can influence SON neurons through an influence on MS-DBB neurons.

scholarly journals The neural basis of temporal individuation and its capacity limits in the human brain

2017 ◽  
Vol 118 (5) ◽  
pp. 2601-2613
Author(s):  
Claire K. Naughtin ◽  
Benjamin J. Tamber-Rosenau ◽  
Paul E. Dux
Keyword(s):  
Human Brain ◽  
Premotor Cortex ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Repetition Blindness ◽  
Neural Basis ◽  
Related Factors ◽  
Regional Patterns ◽  
Repetition Suppression ◽  
Capacity Limit

Individuation refers to individualsʼ use of spatial and temporal properties to register objects as distinct perceptual events relative to other stimuli. Although behavioral studies have examined both spatial and temporal individuation, neuroimaging investigations have been restricted to the spatial domain and at relatively late stages of information processing. Here, we used univariate and multivoxel pattern analyses of functional MRI data to identify brain regions involved in individuating temporally distinct visual items and the neural consequences that arise when this process reaches its capacity limit (repetition blindness, RB). First, we found that regional patterns of blood-oxygen-level-dependent activity across the cortex discriminated between instances where repeated and nonrepeated stimuli were successfully individuated—conditions that placed differential demands on temporal individuation. These results could not be attributed to repetition suppression or other stimulus-related factors, task difficulty, regional activation differences, other capacity-limited processes, or artifacts in the data or analyses. Contrary to current theoretical models, this finding suggests that temporal individuation is supported by a distributed set of brain regions, rather than a single neural correlate. Second, conditions that reflect the capacity limit of individuation—instances of RB—lead to changes in the spatial patterns within this network, as well as amplitude changes in the left hemisphere premotor cortex, superior medial frontal cortex, anterior cingulate cortex, and bilateral parahippocampal place area. These findings could not be attributed to response conflict/ambiguity and likely reflect the core brain regions and mechanisms that underlie the capacity-limited process that gives rise to RB.NEW & NOTEWORTHY We present novel findings into the neural bases of temporal individuation and repetition blindness (RB)—the perceptual deficit that arises when this process reaches its capacity limit. Specifically, we found that temporal individuation is a widely distributed process in the brain and identified a number of candidate brain regions that appear to underpin RB. These findings enhance our understanding of how these fundamental perceptual processes are reflected in the human brain.

Abstract 211: Delayed Cell Death in CA1 Region in a Cardiac Arrest Rat Model: Continuing After 2 Weeks of Survival?

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sandra Högler ◽  
Ursula Teubenbacher ◽  
Wolfgang Weihs ◽  
Fritz Sterz ◽  
Ingrid A M Magnet ◽  
...  
Keyword(s):  
Cell Death ◽  
Cardiac Arrest ◽  
Brain Regions ◽  
Spontaneous Circulation ◽  
Sprague Dawley ◽  
Ca1 Region ◽  
Delayed Cell Death ◽  
Time Period ◽  
Sprague Dawley Rats ◽  
Hematoxylin Eosin

Background: Evolution of histological lesions in selectively vulnerable brain regions in animal models of cardiac arrest (CA)give evidence of potential therapeutic windows. Delayed cell death is of special interest in this regard. Methods: In male Sprague-Dawley rats (350g) ventricular fibrillation (VF) CA was induced for 6 min followed by chest compressions, ventilation and drugs for 2 min. To achieve return of spontaneous circulation animals were defibrillated every 2 min. Animals were sacrificed after one week (n=5) or two weeks (n=7) of survival and compared to four sham animals. Brains were fixed in formalin, embedded in paraffin wax and cut into 3 μm thick coronary sections for histological examination. Viable neurons with nucleolus were counted in Hematoxylin-Eosin (HE)-stained sections in a 250 μm sector of the medial CA1 region. FluoroJade B staining was applied to count dying neurons in the same sector. Results: In HE-staining sham animals had 31±4 viable neurons. In one week survivors 11±9 viable neurons (p=0.003) and in two week survivors 7±7 viable neurons (p=0.001 vs sham, p=0.49 vs one week survivors) were counted. Furthermore, a lot of degenerated hypereosinophilic neurons were present in HE-staining in both CA-groups. FluoroJade B-staining was negative in sham animals. In one week survivors 29±8 dying neurons (p=0.006) and in two week survivors 33±13 dying neurons (p= 0.016 vs sham, p=0.343 vs one week survivors) were detectable. Conclusions: Consistent damage in the medial CA1 region was present after 6 min VFCA in both survival time groups. Lesions seemed to be constant, with no significant differences between time points. Contrary to expectations, FluoroJade B-staining was still positive after two weeks of survival, suggesting that delayed cell death might go on for a longer time period than assumed so far.

scholarly journals Perfluorocarbons Enhance a T2*-Based MRI Technique for Identifying the Penumbra in a Rat Model of Acute Ischemic Stroke

2013 ◽  
Vol 33 (9) ◽  
pp. 1422-1428 ◽  
Author(s):  
Graeme A Deuchar ◽  
David Brennan ◽  
Hugh Griffiths ◽  
I Mhairi Macrae ◽  
Celestine Santosh
Keyword(s):  
Acute Stroke ◽  
Region Of Interest ◽  
Sprague Dawley ◽  
Stroke Patients ◽  
Sprague Dawley Rats ◽  
Signal Change ◽  
Magnetic Resonance Imaging Mri ◽  
Tissue Recovery ◽  
Inspired Oxygen ◽  
Accurate Imaging

Accurate imaging of ischemic penumbra is crucial for improving the management of acute stroke patients. T2* magnetic resonance imaging (MRI) combined with a T2*oxygen challenge (T2*OC) is being developed to detect penumbra based on changes in blood deoxyhemoglobin. Using 100% O2, T2*OC-defined penumbra exhibits ongoing glucose metabolism and tissue recovery on reperfusion. However, potential limitations in translating this technique include a sinus artefact in human scans with delivery of 100% OC and relatively small signal changes. Here we investigate whether an oxygen-carrying perfluorocarbon (PFC) emulsion can enhance the sensitivity of the technique, enabling penumbra detection with lower levels of inspired oxygen. Stroke was induced in male Sprague-Dawley rats ( n =17) with ischemic injury and perfusion deficit determined by diffusion and perfusion MRI, respectively. T2* signal change was measured in regions of interest (ROIs) located within ischemic core, T2*OC-defined penumbra and equivalent contralateral areas during 40% O2± prior PFC injection. Region of interest analyses between groups showed that PFC significantly enhanced the T2* response to 40% O2 in T2*-defined penumbra (mean increase of 10.6 ± 2.3% compared to 5.6 ± 1.5% with 40% O2, P<0.001). This enhancement was specific to the penumbra ROI. Perfluorocarbon emulsions therefore enhances the translational potential of the T2*OC technique for identifying penumbra in acute stroke patients.

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