Peptides and blood-brain barrier transport

Ermisch, A.; Brust, Peter; Kretzschmar, R.; Rühle, H

doi:10.1152/physrev.1993.73.3.489

Cited by 73 publications

(37 citation statements)

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“…Two important issues that need to be clarified is whether peripherally administered OT reaches the brain because of its very limited passage through the blood/brain barrier (BBB) (39), and the brain OT levels required to have a mnemonic effect. Small amounts of OT may cross the BBB (40), and it has been calculated that .002% of SC or intravenous OT reaches the cerebrospinal fluid (CSF) of freely moving rats within 10 minutes of administration.…”

Section: Oxytocin In Learning and Memorymentioning

confidence: 99%

Learning About Oxytocin: Pharmacologic and Behavioral Issues

Chini

Leonzino

Braida

et al. 2014

Biological Psychiatry

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Despite the accumulating evidence suggesting that the neuropeptide oxytocin (OT) plays a role in neuropsychiatric disorders characterized by social dysfunction, the influence of OT on the nonsocial aspects of learning and memory have been less investigated. To foster research in this area, we review the effects of OT on learning and memory in animal models and humans. In healthy animal models, OT improves memory consolidation and extinction, but only if given at a low dose immediately after the acquisition phase. On the contrary, OT effects in healthy humans have been inconsistent; although, in this case, OT was always given before the acquisition phase and no dose-response curves have ever been drawn up. Interestingly, a specific impairment in the reversal of learning has been found in mice devoid of OT receptors and OT has been demonstrated to enhance fear extinction in rodents. All together, these data suggest that OT plays a role in elementary forms of behavioral flexibility and adaptive responses and support its therapeutic potential in neuropsychiatric disorders characterized by cognitive inflexibility and/or impairment (autism, schizophrenia, Alzheimer's disease, Parkinson disease, stroke, posttraumatic stress disorder). Accordingly, OT has been shown to improve cognitive flexibility in OT receptordeficient mice, and scattered findings indicate that intranasal OT has positive effects on the memory of patients with schizophrenia or posttraumatic stress disorders. Further studies of the therapeutic potential of OT as an enhancer of learning and memory are warranted.

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Section: Oxytocin In Learning and Memorymentioning

confidence: 99%

Learning About Oxytocin: Pharmacologic and Behavioral Issues

Chini

Leonzino

Braida

et al. 2014

Biological Psychiatry

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“…In our previous study, oxytocin was given SC, and it was assumed that in enters the brain to directly interact with central oxytocin receptors. However, there is doubt as to whether oxytocin readily crosses the bloodbrain barrier in amounts sufficient to exert effects directly in the central nervous system (Ermisch et al, 1993;Mens et al, 1983). Thus, the focus of the current investigation is to examine the effect of oxytocin administered ICV 30 min before fear-potentiated startle testing, in order to determine if the effects seen mirror those of systemic administration.…”

Section: Introductionmentioning

confidence: 99%

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm: Peripheral vs Central Administration

Ayers

Missig

Schulkin

et al. 2011

Neuropsychopharmacol

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Oxytocin is known to have anti-anxiety and anti-stress effects. Using a fear-potentiated startle paradigm in rats, we previously demonstrated that subcutaneously administered oxytocin suppressed acoustic startle following fear conditioning compared with startle before fear conditioning (termed background anxiety), but did not have an effect on cue-specific fear-potentiated startle. The findings suggest oxytocin reduces background anxiety, an anxious state not directly related to cue-specific fear, but sustained beyond the immediate threat. The goal of the present study was to compare the effects of centrally and peripherally administered oxytocin on background anxiety and cue-specific fear. Male rats were given oxytocin either subcutaneously (SC) or intracerebroventricularly (ICV) into the lateral ventricles before fear-potentiated startle testing. Oxytocin doses of 0.01 and 0.1 mg/kg SC reduced background anxiety. ICV administration of oxytocin at doses from 0.002 to 20 mg oxytocin had no effect on background anxiety or cue-specific fearpotentiated startle. The 20 mg ICV dose of oxytocin did reduce acoustic startle in non-fear conditioned rats. These studies indicate that oxytocin is potent and effective in reducing background anxiety when delivered peripherally, but not when delivered into the cerebroventricular system. Oxytocin given systemically may have anti-anxiety properties that are particularly germane to the hypervigilance and exaggerated startle typically seen in many anxiety and mental health disorder patients.

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“…1,Chapter 5;ref. 2), but the use of these peptide neuromodulators as pharmaceuticals is limited by the bloodbrain barrier (BBB), which excludes most peptides from the brain (3,4), although several enkephalin analogues have been shown to produce effects when administered peripherally (5). The vast potential for naturally occurring brain peptides and their unnatural analogues to alleviate diverse neurological conditions ranging from headaches and anxiety to Alzheimer disease and stroke is now widely recognized (ref.…”

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confidence: 99%

Glycopeptide enkephalin analogues produce analgesia in mice: evidence for penetration of the blood-brain barrier.

Polt

Porreca²,

Szabó

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

222

154

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Most peptides have not proved useful as neuroactive drugs because they are blocked by the blood-brain barrier and do not reach their receptors within the brain.Intraperitoneally administered L-serinyl JD-glucosde aalgues of [Metslenkephaln (glycopeptides) have been shown to be transported across the blood-brain barrier to bind with targeted p and &oplod receptors in the mouse brain. The opioid nature of the bing has been demonstrated with intracerebroventricularly a ered naloxone. Paradoxically, glucosylation decreases the ipophlt of the peptides while promoting transport across the phc endothe layer. It is suggested that glucose transporter GLUT-1 is responsible for the transport of the peptide message. Profound and long-lasting anesla has been observed in mice (tail-ck and hot-plate assays) with two of the glycopeptide a ues when administered intraperitoneally.

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Peptides and blood-brain barrier transport

Cited by 73 publications

References 0 publications

Learning About Oxytocin: Pharmacologic and Behavioral Issues

Learning About Oxytocin: Pharmacologic and Behavioral Issues

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm: Peripheral vs Central Administration

Glycopeptide enkephalin analogues produce analgesia in mice: evidence for penetration of the blood-brain barrier.

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