Lucas Barretto-de-Souza, Shemar A Joseph, Francesca M Lynch, Alexandra J Ng, Carlos C Crestani, John P Christianson
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引用次数: 0
Abstract
Rationale: In a social context, individuals are able to detect external information from others and coordinate behavioral responses according to the situation, a phenomenon called social decision-making. Social decision-making is multifaceted, influenced by emotional and motivational factors like stress, sickness, and hunger. However, the neurobiological basis for motivational state competition and interaction is not well known.
Objective: We investigated possible neural mechanisms through which internal states could shape social behavior in a social affective preference (SAP) test. In the SAP test, experimental rats given a choice to interact with naïve or stressed conspecifics exhibit an age-dependent preference to interact with stressed juvenile conspecifics, but avoid stressed adult conspecifics. First, we assessed the effect of food and water deprivation on SAP behavior. Behavior in the SAP test requires the insular cortex, which receives input from the ingestion-related peptides melanin-concentrating hormone (MCH) and orexin neurons of the lateral hypothalamus (LH). This study aimed to evaluate the role of LH and insular MCH and orexin in SAP test.
Methods: SAP tests were conducted in rats that were sated, food and water deprived or allowed 1 h of access to food and water after 14 h of deprivation (relieved condition). Separate cohorts of sated rats received cannula implants for microinjection of drugs to inhibit the LH or to block or stimulate MCH or orexin receptors in the insula prior to SAP tests or social interaction tests.
Results: Food and water deprivation prior to SAP tests with juvenile rats caused a shift in preference away from the stressed rat toward the naïve juveniles. Pharmacological inhibition of LH with muscimol (100 ng/side) abolished the preference for the juvenile-stressed conspecific, as well as the preference for the adult naïve conspecific. The blockade of MCH receptor 1or orexin receptors in the insular cortex with SNAP94847 (50 μM) or TCS1102 (1 μM), respectively, also abolished the preference for the stressed juvenile conspecific, but only the antagonism of orexin receptors was able to abolish the preference for the adult naïve conspecific. Microinjection of increasing doses (50 or 500 nM) of MCH or orexin-A in the insular cortex increased the interaction time in the one-on-one social interaction test with juvenile conspecifics; however, only the microinjection of orexin-A increased the interaction time with adult naïve conspecifics.
Conclusions: Taken together, these results suggest that lateral hypothalamus peptides shape the direction of social approach or avoidance via actions MCH and orexin neurotransmission in the insular cortex.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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