Sniffing neuropeptides: a transnasal approach to the human brain

Born, Jan; Lange, Tanja; Kern, Werner; McGregor, GP; Bickel, Ulrich; Fehm, Horst L.

doi:10.1038/nn0602-849

Cited by 1,144 publications

(688 citation statements)

References 13 publications

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“…OT, a large molecule peptide, is unable to cross the blood brain barrier if administered peripherally. However, an early study in humans showed that a related peptide, vasopressin, was able to achieve central penetrance after IN administration (Born et al, 2002), possibly through a "direct transport route" where OT obtains rapid access to the CNS through numerous perineuronal spaces in the nasal cavity where it can then enter the CSF (Veening and Olivier, 2013). Moreover, a recent study has now reported that IN-OT administration in humans does increase central concentrations of OT (Striepens et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Because of these prosocial effects, the oxytocinergic system has emerged as a leading target for the development of novel pharmacotherapies for treating social impairments, like those seen in autism spectrum disorders (ASD; Guastella and MacLeod, 2012;Modi and Young, 2012). Although nonapeptides, like OT and vasopression, are large molecular weight compounds that do not readily cross the blood brain barrier when given peripherally, several studies have now confirmed the effectiveness of an intranasal (IN) administration route for delivering these compounds to the central nervous system (CNS) in humans and animals (Born et al, 2002;Chang et al, 2012;Neumann et al, 2013;Striepens et al, 2013;Modi et al, 2014). Using this method, studies have reported broad effects of OT on the perception of social stimuli including increasing the salience of the eyes in faces (Guastella et al, 2008;Andari et al, 2010), altering the perception of facial expressions (Domes et al, 2007a,b;Fischer-Shofty et al, 2010;Gamer et al, 2010;Parr et al, 2013), enhancing memory for face identity (Savaskan et al, 2008;Rimmele et al, 2009), and decreasing social vigilance (Ebitz et al, 2013).…”

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confidence: 99%

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Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys

Parr

2014

Front. Behav. Neurosci.

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There are currently no drugs approved for the treatment of social deficits associated with autism spectrum disorders (ASD). One hypothesis for these deficits is that individuals with ASD lack the motivation to attend to social cues because those cues are not implicitly rewarding. Therefore, any drug that could enhance the rewarding quality of social stimuli could have a profound impact on the treatment of ASD, and other social disorders. Oxytocin (OT) is a neuropeptide that has been effective in enhancing social cognition and social reward in humans. The present study examined the ability of OT to selectively enhance learning after social compared to nonsocial reward in rhesus monkeys, an important species for modeling the neurobiology of social behavior in humans. Monkeys were required to learn an implicit visual matching task after receiving either intranasal (IN) OT or Placebo (saline). Correct trials were rewarded with the presentation of positive and negative social (play faces/threat faces) or nonsocial (banana/cage locks) stimuli, plus food. Incorrect trials were not rewarded. Results demonstrated a strong effect of sociallyreinforced learning, monkeys' performed significantly better when reinforced with social vs. nonsocial stimuli. Additionally, socially-reinforced learning was significantly better and occurred faster after IN-OT compared to placebo treatment. Performance in the IN-OT, but not Placebo, condition was also significantly better when the reinforcement stimuli were emotionally positive compared to negative facial expressions. These data support the hypothesis that OT may function to enhance prosocial behavior in primates by increasing the rewarding quality of emotionally positive, social compared to emotionally negative or nonsocial images. These data also support the use of the rhesus monkey as a model for exploring the neurobiological basis of social behavior and its impairment.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys

Parr

2014

Front. Behav. Neurosci.

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“…This phenomenon may be attributed to intranasal administration. Several studies (Arora et al, 2002;Born et al, 2002;Costantino et al, 2007) have shown that a drug to reach the CNS from the nasal cavity will have to cross the olfactory membrane and the arachnoid membrane surrounding the arachnoid space containing the cerebro-spinal fluid. The drug can also be absorbed across the nasal mucosa and reach the systemic circulation to reach the brain by crossing the BBB.…”

Section: Discussionmentioning

confidence: 99%

Comparative pharmacokinetic studies of borneol in mouse plasma and brain by different administrations

Zhao

et al. 2012

J. Zhejiang Univ. Sci. B

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Borneol, a monoterpenoid alcohol, is used widely, particularly in combined formulas for preventing and curing cardiovascular and cerebrovascular diseases in traditional Chinese medicine. In order to understand the blood and brain pharmacokinetics after intravenous, intranasal, or oral administration and to investigate the superiority and feasibility of intranasal administration, a simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the quantification of borneol. Blood samples and brain were collected from mice at 1, 3, 5, 10, 20, 30, 60, 90, and 120 min after intravenous, intranasal, or oral administration of borneol at a dosage of 30.0 mg/kg. Sample preparations were carried out by liquid-liquid extraction with an internal standard solution of octadecane. The pharmacokinetic parameters were calculated by the software of Kinetica. The calibration curves were linear in the range of 0.11-84.24 μg/ml and 0.16-63.18 μg/g for borneol in plasma and brain, respectively. The methodological and extraction recoveries were both in the range of 85%-115%. The intra-day and inter-day variabilities for plasma and brain samples were ≤5.00% relative standard deviation (RSD). The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%. The relative brain targeted coefficients Re of intranasal and oral administrations were 68.37% and 38.40%. The GC-FID method developed could be applied to determination and pharmacokinetic study. The borneol from injection was distributed and metabolized fast without absorption process. The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability. Nasal administration of borneol was quickly absorbed into the blood and brain, was easy to use and had a greater safety than infection, which makes it worthy of further development as an administration route for encephalopathy treatment.

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“…Since the effects of insulin and glucose in human studies are difficult to differentiate, we used the intranasal administration of insulin. This technique allowed us to study central insulin action by selective delivery of the hormone into the brain, without relevant effects on peripheral glucose concentrations [15]. After intranasal insulin administration, insulin enters the cerebrospinal fluid compartment and influences brain function, demonstrating for example beneficial effects on memory functions and promoting weight loss [16,17,18,19].…”

Section: Introductionmentioning

confidence: 99%

Intranasal Insulin Modulates Intrinsic Reward and Prefrontal Circuitry of the Human Brain in Lean Women

Kullmann¹,

Frank

Heni

et al. 2012

Neuroendocrinology

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Aim: There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. Methods: We performed ‘resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Results: Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. Conclusion: This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy.

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Sniffing neuropeptides: a transnasal approach to the human brain

Cited by 1,144 publications

References 13 publications

Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys

Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys

Comparative pharmacokinetic studies of borneol in mouse plasma and brain by different administrations

Intranasal Insulin Modulates Intrinsic Reward and Prefrontal Circuitry of the Human Brain in Lean Women

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