Synthesis and evaluation of C-11, F-18 and I-125 small molecule radioligands for detecting oxytocin receptors

Smith, Aaron L.; Freeman, Sara M.; Stehouwer, Jeffery S.; Inoue, Kiyoshi; Voll, Ronald J.; Young, Larry J.; Goodman, Mark M.

doi:10.1016/j.bmc.2012.02.019

Cited by 33 publications

(29 citation statements)

References 33 publications

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“…Analyses of human tissue have used ligands promiscuous for both OTR and AVPR1a [15], but have reported high densities in the VP [16]. It will be important to re-analyze human tissue using more sensitive and selective techniques; however, to the best of our knowledge, every socially monogamous species examined to date has exhibited high OTR and/or AVPR1a expression in the NAcc-VP circuit; these data encourage further research on neuropeptidergic regulation of this circuit in the evolution of social bonding.…”

Section: Social Neuropeptides In Pair Bondingmentioning

confidence: 99%

Neurobiological mechanisms of social attachment and pair bonding

Johnson

Young

2015

Current Opinion in Behavioral Sciences

153

138

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Species have evolved diverse social behavior and mating strategies in response to selective forces in their environments. While promiscuity is the predominant mating strategy across most vertebrate taxa, convergent evolution of monogamous mating systems has occurred multiple times across distant lineages. Monogamous behavior is thought to be facilitated by a neurobiological capacity to form and maintain selective social attachments, or pair bonds, with a mating partner. The neural mechanisms of pair bonding behavior have been investigated most rigorously in Microtine rodents, which exhibit diverse social organizations. These studies have highlighted mesolimbic dopamine pathways, social neuropeptides (oxytocin and vasopressin), and other neural systems as integral factors in the formation, maintenance, and expression of pair bonds.

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Section: Social Neuropeptides In Pair Bondingmentioning

confidence: 99%

Neurobiological mechanisms of social attachment and pair bonding

Johnson

Young

2015

Current Opinion in Behavioral Sciences

153

138

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“…Ongoing clinical trials will do well to include life history variables, environmental context, and consider the potential contribution of individual differences in the genetics of these signaling pathways. As a result of the limitations of human research, we could use better biomarkers and a clear picture of the distribution of OXTR and V1aR in human tissue via the development of selective PET ligands (Smith et al, 2012), and endophenotype approaches to gene-brain-behavior relationships (Haas et al, 2013).…”

Section: Future Research Directionsmentioning

confidence: 99%

Developmental Perspectives on Oxytocin and Vasopressin

Hammock

2014

Neuropsychopharmacol

153

146

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The related neuropeptides oxytocin and vasopressin are involved in species-typical behavior, including social recognition behavior, maternal behavior, social bonding, communication, and aggression. A wealth of evidence from animal models demonstrates significant modulation of adult social behavior by both of these neuropeptides and their receptors. Over the last decade, there has been a flood of studies in humans also implicating a role for these neuropeptides in human social behavior. Despite popular assumptions that oxytocin is a molecule of social bonding in the infant brain, less mechanistic research emphasis has been placed on the potential role of these neuropeptides in the developmental emergence of the neural substrates of behavior. This review summarizes what is known and assumed about the developmental influence of these neuropeptides and outlines the important unanswered questions and testable hypotheses. There is tremendous translational need to understand the functions of these neuropeptides in mammalian experience-dependent development of the social brain. The activity of oxytocin and vasopressin during development should inform our understanding of individual, sex, and species differences in social behavior later in life.

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“…While localization of OT receptors have yet to be definitively mapped in primates and humans (Toloczko et al, 1997), efforts are being made to develop a radioligand that will bind with high specificity to human OT receptors (Smith et al, 2012). Distribution patterns of OT receptors across brain areas are highly species dependent (Insel and Shapiro, 1992; Young et al, 1996), and binding sites are up-regulated in specific areas in response to peripheral (such as pregnancy) or environmental (such as social cooperation) cues (Viero et al, 2010).…”

Section: Intranasal Delivery: Mechanismsmentioning

confidence: 99%

Intranasal oxytocin effects on social cognition: A critique

et al. 2014

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The last decade has seen a large number of published findings supporting the hypothesis that intranasally delivered oxytocin (OT) can enhance the processing of social stimuli and regulate social emotion-related behaviors such as trust, memory, fidelity, and anxiety. The use of nasal spray for administering OT in behavioral research has become a standard method, but many questions still exist regarding its action. OT is a peptide that cannot cross the blood-brain barrier, and it has yet to be shown that it does indeed reach the brain when delivered intranasally. Given the evidence, it seems highly likely that OT does affect behavior when delivered as a nasal spray. These effects may be driven by at least three possible mechanisms. First, the intranasally delivered OT may diffuse directly into the CNS where it directly engages OT receptors. Second, the intranasally delivered OT may trigger increased central release via an indirect peripheral mechanism. And third, the indirect peripheral effects may directly lead to behavioral effects via some mechanism other than increased central release. Although intranasally delivered OT likely affects behavior, there are conflicting reports as to the exact nature of those behavioral changes: some studies suggest that OT effects are not always “pro-social” and others suggest effects on social behaviors are due to a more general anxiolytic effect. In this critique, we draw from work in healthy human populations and the animal literature to review the mechanistic aspects of intranasal OT delivery, and to discuss intranasal OT effects on social cognition and behavior. We conclude that future work should control carefully for anxiolytic and gender effects, which could underlie inconsistencies in the existing literature.

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Synthesis and evaluation of C-11, F-18 and I-125 small molecule radioligands for detecting oxytocin receptors

Cited by 33 publications

References 33 publications

Neurobiological mechanisms of social attachment and pair bonding

Neurobiological mechanisms of social attachment and pair bonding

Developmental Perspectives on Oxytocin and Vasopressin

Intranasal oxytocin effects on social cognition: A critique

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