Data from: Disruption of the CRF1 receptor eliminates morphine-induced sociability deficits and firing of oxytocinergic neurons in male mice
Data files
Feb 07, 2025 version files 91.53 KB
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Piccin_et_al._eLife_2024_for_Dryad.xls
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README.md
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Abstract
Substance-induced social behavior deficits dramatically worsen the clinical outcome of substance use disorders; yet, the underlying mechanisms remain poorly understood. Herein, we investigated the role for the corticotropin-releasing factor receptor 1 (CRF1) in the acute sociability deficits induced by morphine and the related activity of oxytocin (OXY)- and arginine-vasopressin (AVP)-expressing neurons of the paraventricular nucleus of the hypothalamus (PVN). For this purpose, we used both the CRF1 receptor-preferring antagonist compound antalarmin and the genetic mouse model of CRF1 receptor-deficiency. Antalarmin completely abolished sociability deficits induced by morphine in male, but not in female, C57BL/6J mice. Accordingly, genetic CRF1 receptor-deficiency eliminated morphine-induced sociability deficits in male mice. Ex vivo electrophysiology studies showed that antalarmin also eliminated morphine-induced firing of PVN neurons in male, but not in female, C57BL/6J mice. Likewise, genetic CRF1 receptor-deficiency reduced morphine-induced firing of PVN neurons in a CRF1 gene expression-dependent manner. The electrophysiology results consistently mirrored the behavioral results, indicating a link between morphine-induced PVN activity and sociability deficits. Interestingly, in male mice antalarmin abolished morphine-induced firing in neurons co-expressing OXY and AVP, but not in neurons expressing only AVP. In contrast, in female mice antalarmin did not affect morphine-induced firing of neurons co-expressing OXY and AVP or only OXY, indicating a selective sex-specific role for the CRF1 receptor in opiate-induced PVN OXY activity. The present findings demonstrate a major, sex-linked, role for the CRF1 receptor in sociability deficits and related brain alterations induced by morphine, suggesting new therapeutic strategy for opiate use disorders.
Description of the file and data structure:
This dataset consists of a data file named: Piccin_et_al._eLife_2024_for_Dryad
Table 1 – 3CH C57 males
This tab contains the behavioral data reported in Figure 1B and Figure 1 – figure supplement 1A
“3CH” stands for “three-chamber”, “C57” stands for “C57BL/6“
“subject” = ID number of the subject animal
“pretreat” = pre-treatement received (either “veh” = vehicle or “anta” = antalarmin 20 mg/kg p.o.)
“treat” = treatment received (either “sal” = saline or “mor” = morphine 2.5 mg/kg i.p.)
“P” stands for “Phase”, “S” stands for “Side”
“P1_S1” = time spent (sec) on the mouse half-chamber during the habituation phase (empty)
“P1_S2” = time spent (sec) on the object half-chamber during the habituation phase (empty)
“P2_S1” = time spent (sec) on the mouse half-chamber during the sociability phase
“P2_S2” = time spent (sec) on the object half-chamber during the sociability phase
“soc ratio” = % of time spent with the mouse, calculated as [P2_S1/(P2_S1+P2_S2)]*100
“loco hab” = distance travelled (meters) by the subject mouse during the habituation phase
“loco soc” = distance travelled (meters) by the subject mouse during the sociability phase
In red and bold are noted the mean and the SEM of the data in the corresponding column
Table 2 – 3CH C57 females
This tab contains the behavioral data reported in Figure 1C and Figure 1 – figure supplement 1B
“3CH” stands for “three-chamber”, “C57” stands for “C57BL/6“
“subject” = ID number of the subject animal
“pretreat” = pre-treatement received (either “veh” = vehicle or “anta” = antalarmin 20 mg/kg p.o.)
“treat” = treatment received (either “sal” = saline or “mor” = morphine 2.5 mg/kg i.p.)
“P” stands for “Phase”, “S” stands for “Side”
“P1_S1” = time spent (sec) on the mouse half-chamber during the habituation phase (empty)
“P1_S2” = time spent (sec) on the object half-chamber during the habituation phase (empty)
“P2_S1” = time spent (sec) on the mouse half-chamber during the sociability phase
“P2_S2” = time spent (sec) on the object half-chamber during the sociability phase
“soc ratio” = % of time spent with the mouse, calculated as [P2_S1/(P2_S1+P2_S2)]*100
“loco hab” = distance travelled (meters) by the subject mouse during the habituation phase
“loco soc” = distance travelled (meters) by the subject mouse during the sociability phase
In red and bold are noted the mean and the SEM of the data in the corresponding column
Table 3 – 3CH CRF1 KO males
This tab contains the behavioral data reported in Figure 3B and Figure 3 – figure supplement 1
“3CH” stands for “three-chamber”, “CRF1” stands for “CRF1 mice“
“subject” = ID number of the subject animal
“geno” = genotype (either “WT” = wild-type, “HET” = heterozygous, or “KO” = knock-out)
“treat” = treatment received (either “SAL” = saline or “MOR” = morphine 0.625 mg/kg i.p.)
“P” stands for “Phase”, “S” stands for “Side”
“P1_S1” = time spent (sec) on the mouse half-chamber during the habituation phase (empty)
“P1_S2” = time spent (sec) on the object half-chamber during the habituation phase (empty)
“P2_S1” = time spent (sec) on the mouse half-chamber during the sociability phase
“P2_S2” = time spent (sec) on the object half-chamber during the sociability phase
“soc ratio” = % of time spent with the mouse, calculated as [P2_S1/(P2_S1+P2_S2)]*100
“loco hab” = distance travelled (meters) by the subject mouse during the habituation phase
“loco soc” = distance travelled (meters) by the subject mouse during the sociability phase
In red and bold are noted the mean and the SEM of the data in the corresponding column
Table 4 – Ephy C57 males
This tab contains the electrophysiological data reported in Figure 2B and Figure 4C-D
“Ephy” stands for “electrophysiology”, “C57” stands for “C57BL/6“
“veh” stands for “vehicle”, “anta” stands for “antalarmin” (20 mg/kg p.o.)
“sal” stands for “saline”, “mor” stands for “morphine” (2.5 mg/kg i.p.)
“ALL CELLS” corresponds to the data in Figure 2B
“OXY-AVP” corresponds to the data in Figure 4C
“AVP” corresponds to the data in Figure 4D
“OXY” stands for “oxytocin”, “AVP” stands for “vasopressin”
In red and bold are noted the mean and the SEM of the data in the corresponding column
Table 5 – Ephy C57 females
This tab contains the electrophysiological data reported in Figure 2D and Figure 4F-G
“Ephy” stands for “electrophysiology”, “C57” stands for “C57BL/6“
“veh” stands for “vehicle”, “anta” stands for “antalarmin” (20 mg/kg p.o.)
“sal” stands for “saline”, “mor” stands for “morphine” (2.5 mg/kg i.p.)
“ALL CELLS” corresponds to the data in Figure 2D
“OXY-AVP” corresponds to the data in Figure 4F
“OXY” highlighted in yellow corresponds to the data in Figure 4G
“OXY” stands for “oxytocin”, “AVP” stands for “vasopressin”
In red and bold are noted the mean and the SEM of the data in the corresponding column
Table 6 – Ephy CRF1 KO males
This tab contains the electrophysiological data reported in Figure 3E
“Ephy” stands for “electrophysiology”, “CRF1” stands for “CRF1 mice“
“wt” = wild-type, “het” = heterozygous, or “ko” = knock-out
“sal” = “saline”, “mor” = “morphine” (0.625 mg/kg i.p.)
“ALL CELLS” corresponds to the data in Figure 3E
In red and bold are noted the mean and the SEM of the data in the corresponding column